A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure.
A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia.
Immature ERYTHROCYTES. In humans, these are ERYTHROID CELLS that have just undergone extrusion of their CELL NUCLEUS. They still contain some organelles that gradually decrease in number as the cells mature. RIBOSOMES are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic "reticulum" (not the same as the ENDOPLASMIC RETICULUM), hence the name reticulocytes.
A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.
Members of the alpha-globin family. In humans, they are encoded in a gene cluster on CHROMOSOME 16. They include zeta-globin and alpha-globin. There are also pseudogenes of zeta (theta-zeta) and alpha (theta-alpha) in the cluster. Adult HEMOGLOBIN is comprised of 2 alpha-globin chains and 2 beta-globin chains.
Members of the beta-globin family. In humans, they are encoded in a gene cluster on CHROMOSOME 11. They include epsilon-globin, gamma-globin, delta-globin and beta-globin. There is also a pseudogene of beta (theta-beta) in the gene cluster. Adult HEMOGLOBIN is comprised of two ALPHA-GLOBIN chains and two beta-globin chains.
The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements.
A regulatory region first identified in the human beta-globin locus but subsequently found in other loci. The region is believed to regulate GENETIC TRANSCRIPTION by opening and remodeling CHROMATIN structure. It may also have enhancer activity.
Genes that cause the epigenotype (i.e., the interrelated developmental pathways through which the adult organism is realized) to switch to an alternate cell lineage-related pathway. Switch complexes control the expression of normal functional development as well as oncogenic transformation.
Chloro(7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropanoato(4-)-N(21),N(22),N(23),N(24)) ferrate(2-) dihydrogen.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A group of inherited disorders characterized by structural alterations within the hemoglobin molecule.
The production of red blood cells (ERYTHROCYTES). In humans, erythrocytes are produced by the YOLK SAC in the first trimester; by the liver in the second trimester; by the BONE MARROW in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction.
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent.
The series of cells in the red blood cell lineage at various stages of differentiation.
Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)
Immature, nucleated ERYTHROCYTES occupying the stage of ERYTHROPOIESIS that follows formation of ERYTHROID PRECURSOR CELLS and precedes formation of RETICULOCYTES. The normal series is called normoblasts. Cells called MEGALOBLASTS are a pathologic series of erythroblasts.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Members of the beta-globin family. In humans, two non-allelic types of gamma-globin - A gamma and G gamma are encoded in the beta-globin gene cluster on CHROMOSOME 11. Two gamma-globin chains combine with two ZETA-GLOBIN chains to form the embryonic hemoglobin Portland. Fetal HEMOGLOBIN F is formed from two gamma-globin chains combined with two ALPHA-GLOBIN chains.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
The cells in the erythroid series derived from MYELOID PROGENITOR CELLS or from the bi-potential MEGAKARYOCYTE-ERYTHROID PROGENITOR CELLS which eventually give rise to mature RED BLOOD CELLS. The erythroid progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E); BFU-E differentiate into CFU-E on stimulation by ERYTHROPOIETIN, and then further differentiate into ERYTHROBLASTS when stimulated by other factors.
The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.
Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains.
A family of hemoglobin-like proteins found in BACTERIA; PLANTS; and unicellular eukaryotes. Truncated hemoglobins are distantly related to vertebrate hemoglobins and are typically shorter than vertebrate hemoglobins by 20-40 residues.
A tissue-specific subunit of NF-E2 transcription factor that interacts with small MAF PROTEINS to regulate gene expression. P45 NF-E2 protein is expressed primarily in MEGAKARYOCYTES; ERYTHROID CELLS; and MAST CELLS.
A disorder characterized by reduced synthesis of the alpha chains of hemoglobin. The severity of this condition can vary from mild anemia to death, depending on the number of genes deleted.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.
A basic-leucine zipper transcription factor that regulates GLOBIN gene expression and is related to TRANSCRIPTION FACTOR AP-1. NF-E2 consists of a small MAF protein subunit and a tissue-restricted 45 kDa subunit.
A group of transcription factors that were originally described as being specific to ERYTHROID CELLS.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation.
Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A disease characterized by chronic hemolytic anemia, episodic painful crises, and pathologic involvement of many organs. It is the clinical expression of homozygosity for hemoglobin S.
An adult hemoglobin component normally present in hemolysates from human erythrocytes in concentrations of about 3%. The hemoglobin is composed of two alpha chains and two delta chains. The percentage of HbA2 varies in some hematologic disorders, but is about double in beta-thalassemia.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Chromosomes in which fragments of exogenous DNA ranging in length up to several hundred kilobase pairs have been cloned into yeast through ligation to vector sequences. These artificial chromosomes are used extensively in molecular biology for the construction of comprehensive genomic libraries of higher organisms.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)
A class of marine annelids including sandworms, tube worms, clamworms, and fire worms. It includes also the genus Myxicola infundibulum.
An abnormal hemoglobin composed of four beta chains. It is caused by the reduced synthesis of the alpha chain. This abnormality results in ALPHA-THALASSEMIA.
A GATA transcription factor that is specifically expressed in hematopoietic lineages and plays an important role in the CELL DIFFERENTIATION of ERYTHROID CELLS and MEGAKARYOCYTES.
An abnormal hemoglobin that results from the substitution of lysine for glutamic acid at position 26 of the beta chain. It is most frequently observed in southeast Asian populations.
A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)
An enzyme capable of hydrolyzing highly polymerized DNA by splitting phosphodiester linkages, preferentially adjacent to a pyrimidine nucleotide. This catalyzes endonucleolytic cleavage of DNA yielding 5'-phosphodi- and oligonucleotide end-products. The enzyme has a preference for double-stranded DNA.
An abnormal hemoglobin resulting from the substitution of valine for glutamic acid at position 6 of the beta chain of the globin moiety. The heterozygous state results in sickle cell trait, the homozygous in sickle cell anemia.
A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group.
A group of adenine ribonucleotides in which the phosphate residues of each adenine ribonucleotide act as bridges in forming diester linkages between the ribose moieties.
An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.
Any cell, other than a ZYGOTE, that contains elements (such as NUCLEI and CYTOPLASM) from two or more different cells, usually produced by artificial CELL FUSION.
Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

Deletion of a region that is a candidate for the difference between the deletion forms of hereditary persistence of fetal hemoglobin and deltabeta-thalassemia affects beta- but not gamma-globin gene expression. (1/3761)

The analysis of a number of cases of beta-globin thalassemia and hereditary persistence of fetal hemoglobin (HPFH) due to large deletions in the beta-globin locus has led to the identification of several DNA elements that have been implicated in the switch from human fetal gamma- to adult beta-globin gene expression. We have tested this hypothesis for an element that covers the minimal distance between the thalassemia and HPFH deletions and is thought to be responsible for the difference between a deletion HPFH and deltabeta-thalassemia, located 5' of the delta-globin gene. This element has been deleted from a yeast artificial chromosome (YAC) containing the complete human beta-globin locus. Analysis of this modified YAC in transgenic mice shows that early embryonic expression is unaffected, but in the fetal liver it is subject to position effects. In addition, the efficiency of transcription of the beta-globin gene is decreased, but the developmental silencing of the gamma-globin genes is unaffected by the deletion. These results show that the deleted element is involved in the activation of the beta-globin gene perhaps through the loss of a structural function required for gene activation by long-range interactions.  (+info)

The splicing factor-associated protein, p32, regulates RNA splicing by inhibiting ASF/SF2 RNA binding and phosphorylation. (2/3761)

The cellular protein p32 was isolated originally as a protein tightly associated with the essential splicing factor ASF/SF2 during its purification from HeLa cells. ASF/SF2 is a member of the SR family of splicing factors, which stimulate constitutive splicing and regulate alternative RNA splicing in a positive or negative fashion, depending on where on the pre-mRNA they bind. Here we present evidence that p32 interacts with ASF/SF2 and SRp30c, another member of the SR protein family. We further show that p32 inhibits ASF/SF2 function as both a splicing enhancer and splicing repressor protein by preventing stable ASF/SF2 interaction with RNA, but p32 does not block SRp30c function. ASF/SF2 is highly phosphorylated in vivo, a modification required for stable RNA binding and protein-protein interaction during spliceosome formation, and this phosphorylation, either through HeLa nuclear extracts or through specific SR protein kinases, is inhibited by p32. Our results suggest that p32 functions as an ASF/SF2 inhibitory factor, regulating ASF/SF2 RNA binding and phosphorylation. These findings place p32 into a new group of proteins that control RNA splicing by sequestering an essential RNA splicing factor into an inhibitory complex.  (+info)

Substrate specificities of SR proteins in constitutive splicing are determined by their RNA recognition motifs and composite pre-mRNA exonic elements. (3/3761)

We report striking differences in the substrate specificities of two human SR proteins, SF2/ASF and SC35, in constitutive splicing. beta-Globin pre-mRNA (exons 1 and 2) is spliced indiscriminately with either SR protein. Human immunodeficiency virus tat pre-mRNA (exons 2 and 3) and immunoglobulin mu-chain (IgM) pre-mRNA (exons C3 and C4) are preferentially spliced with SF2/ASF and SC35, respectively. Using in vitro splicing with mutated or chimeric derivatives of the tat and IgM pre-mRNAs, we defined specific combinations of segments in the downstream exons, which mediate either positive or negative effects to confer SR protein specificity. A series of recombinant chimeric proteins consisting of domains of SF2/ASF and SC35 in various combinations was used to localize trans-acting domains responsible for substrate specificity. The RS domains of SF2/ASF and SC35 can be exchanged without effect on substrate specificity. The RNA recognition motifs (RRMs) of SF2/ASF are active only in the context of a two-RRM structure, and RRM2 has a dominant role in substrate specificity. In contrast, the single RRM of SC35 can function alone, but its substrate specificity can be influenced by the presence of an additional RRM. The RRMs behave as modules that, when present in different combinations, can have positive, neutral, or negative effects on splicing, depending upon the specific substrate. We conclude that SR protein-specific recognition of specific positive and negative pre-mRNA exonic elements via one or more RRMs is a crucial determinant of the substrate specificity of SR proteins in constitutive splicing.  (+info)

A new alkali-resistant hemoglobin alpha2J Oxford gammaF2 in a Sicilian baby girl with homozygous beta0 thalassemia. (4/3761)

A 10-mo-old baby girl with homozygous beta0 thalassemia and alphaJOxford, presenting the clinical picture of homozygous beta thalassemia is described. Hemoglobin electrophoresis showed three bands: the first two with the mobilities of hemoglobin Hb A2 (1%) and Hb F (69%), respectively, the third migrating a little faster than Hb A (30%). About 30% of her alpha chains were J Oxford which, bound to her gamma chains, produced a new alkali-resistant hemoglobin, alpha2 J Oxford gamma F2, which has not been described previously. Hemoglobin synthesis in vitro showed the absence of beta chain synthesis and an alpha/non-alpha ratio of 2. The patient's father was heterozygous for both the Hb J Oxford and beta0 thalassemia genes, the mother a carrier of beta0 thalassemia; four other relatives were carriers of Hb J Oxford, and one was a carrier of beta thalassemia.  (+info)

The identification of ferritin in the nucleus of K562 cells, and investigation of a possible role in the transcriptional regulation of adult beta-globin gene expression. (5/3761)

We studied the subcellular distribution of ferritin in K562 cells by immunofluorescence techniques and have made a reappraisal of a direct binding interaction between ferritin and the proximal promoter region of the human beta-globin gene, as previously mentioned in the literature. Confocal microscopy indicates that ferritin, the iron-storage protein, is present in the nucleus of K562 cells, in addition to its expected cytoplasmic localisation. The stain distribution suggests that it is not directly associated with the nuclear matrix. Using a gel mobility shift assay, a protein that cross-reacts with monoclonal ferritin antibodies competitively binds to a double-stranded oligonucleotide spanning the region situated 150 base pairs upstream from the beta-globin transcription start site. Despite this antibody cross-reactivity, the protein is unlike cytosolic ferritin as it appears to be highly sensitive to both temperature and freeze-thaw cycles, and UV-crosslinking experiments indicate that the molecular mass of the protein factor lies between 90 and 100 kDa. In conclusion, while the intranuclear location of ferritin is described in the present study, ferritin is not in direct contact with the beta-globin promoter region.  (+info)

Pre-mRNA splicing of IgM exons M1 and M2 is directed by a juxtaposed splicing enhancer and inhibitor. (6/3761)

Splicing of certain pre-mRNA introns is dependent on an enhancer element, which is typically purine-rich. It is generally thought that enhancers increase the use of suboptimal splicing signals, and one specific proposal is that enhancers stabilize binding of U2AF65 to weak polypyrimidine (Py) tracts. Here, we test this model using an IgM pre-mRNA substrate, which contains a well-characterized enhancer. Although the enhancer was required for in vitro splicing, we found it had no effect on U2AF65 binding. Unexpectedly, replacement of the natural IgM Py tract, branchpoint, and 5' splice site with consensus splicing signals did not circumvent the enhancer requirement. These observations led us to identify a novel regulatory element within the IgM M2 exon that acts as a splicing inhibitor; removal of the inhibitor enabled splicing to occur in the absence of the enhancer. The IgM M2 splicing inhibitor is evolutionarily conserved, can inhibit the activity of an unrelated, constitutively spliced pre-mRNA, and acts by repressing splicing complex assembly. Interestingly, the inhibitor itself forms an ATP-dependent complex that contains U2 snRNP. We conclude that splicing of IgM exons M1 and M2 is directed by two juxtaposed regulatory elements-an enhancer and an inhibitor-and that a primary function of the enhancer is to counteract the inhibitor.  (+info)

Identification of heparin-binding EGF-like growth factor as a target in intercellular regulation of epidermal basal cell growth by suprabasal retinoic acid receptors. (7/3761)

The role of retinoic acid receptors (RARs) in intercellular regulation of cell growth was assessed by targeting a dominant-negative RARalpha mutant (dnRARalpha) to differentiated suprabasal cells of mouse epidermis. dnRARalpha lacks transcriptional activation but not DNA-binding and receptor dimerization functions. Analysis of transgenic mice revealed that dnRARalpha dose-dependently impaired induction of basal cell proliferation and epidermal hyperplasia by all-trans RA (tRA). dnRARalpha formed heterodimers with endogenous retinoid X receptor-alpha (RXRalpha) over RA response elements in competition with remaining endogenous RARgamma-RXRalpha heterodimers, and dose-dependently impaired retinoid-dependent gene transcription. To identify genes regulated by retinoid receptors and involved in cell growth control, we analyzed the retinoid effects on expression of the epidermal growth factor (EGF) receptor, EGF, transforming growth factor-alpha, heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin genes. In normal epidermis, tRA rapidly and selectively induced expression of HB-EGF but not the others. This induction occurred exclusively in suprabasal cells. In transgenic epidermis, dnRARalpha dose-dependently inhibited tRA induction of suprabasal HB-EGF and subsequent basal cell hyperproliferation. Together, our observations suggest that retinoid receptor heterodimers located in differentiated suprabasal cells mediate retinoid induction of HB-EGF, which in turn stimulates basal cell growth via intercellular signaling. These events may underlie retinoid action in epidermal regeneration during wound healing.  (+info)

Intronless mRNA transport elements may affect multiple steps of pre-mRNA processing. (8/3761)

We have reported recently that a small element within the mouse histone H2a-coding region permits efficient cytoplasmic accumulation of intronless beta-globin cDNA transcripts. This sequence lowers the levels of spliced products from intron-containing constructs and can functionally replace Rev and the Rev-responsive element (RRE) in the nuclear export of unspliced HIV-1-related mRNAs. In work reported here, we further investigate the molecular mechanisms by which this element might work. We demonstrate here through both in vivo and in vitro assays that, in addition to promoting mRNA nuclear export, this element acts as a polyadenylation enhancer and as a potent inhibitor of splicing. Surprisingly, two other described intronless mRNA transport elements (from the herpes simplex virus thymidine kinase gene and hepatitis B virus) appear to function in a similar manner. These findings prompt us to suggest that a general feature of intronless mRNA transport elements might be a collection of phenotypes, including the inhibition of splicing and the enhancement of both polyadenylation and mRNA export.  (+info)

Using the dominant control region (DCR) sequences that flank the beta-globin gene locus, we have been able to achieve high-level expression of the human alpha-globin gene in transgenic mice. Expression in fetal liver and blood is copy number dependent and at levels comparable to that of the endogenous mouse alpha-globin genes. Transgenic fetuses with high-copy numbers of the transgene suffer severe anemia and die before birth. Using a construct with both the human alpha- and beta-globin genes and the beta-globin DCR, live mice with low-copy numbers were obtained. Both human globin genes are expressed at high levels in adult red cells to give human hemoglobin HbA in amounts equal to or greater than endogenous mouse hemoglobin. Expression of HbA in murine red cells is not accompanied by any increase in mean corpuscular volume (MCV) or mean corpuscular hemoglobin concentration (MCHC). However, these transgenic mice tend to have an increased number of reticulocytes in peripheral blood; consistent with some
Previous work has suggested that the promoter regions of the human embryonic zeta 2 and epsilon globin genes contain negative regulatory regions that could play a role in the repression of these genes in postembryonic erythroblasts. We have examined this possibility by studying the expression of these genes in mouse erythroleukemia cells, an adult erythroid cell line that might be expected to contain repressor molecules that would bind to the putative negative regulatory regions. When attached to appropriate upstream regulatory elements (alpha HS-40 and beta HS1,2) both the zeta and epsilon genes were expressed in these cells at a low level, but no increase in expression was observed when similar constructs lacking the proposed negative regulatory sequences were introduced into these cells. These results cast doubt on the possibility that these sequences play a major role in the developmental repression of the embryonic globin genes, unless they function only in a normal chromosomal organization.
Using the dominant control region (DCR) sequences that flank the beta-globin gene locus, we have been able to achieve high-level expression of the human alpha-globin gene in transgenic mice. Expression in fetal liver and blood is copy number dependent and at levels comparable to that of the
We have analysed the effect of a 1.4 kb segment of DNA containing the upstream alpha globin regulatory element (HS-40) on human alpha globin gene expression in fetal mice and lines of transgenic mice. High levels of tissue-specific, human alpha mRNA expression were seen in all transgenic animals and in this sense expression was position independent. However, the level of human alpha mRNA expression per integrated gene copy decreased during development and was inversely related to copy number. The limitation in expression with increasing gene copy number was shown to be in cis since homozygotes for the transgene produced twice as much human alpha mRNA as hemizygotes. In many respects HS -40 appears similar to single elements within the previously described beta globin locus control region and in cross breeding experiments we have shown that HS -40 behaves in a similar manner to such elements in transgenic mice.
Adult White Leghorn chickens were rendered anemic by injection with 1-acetyl-2-phenylhydrazine and then treated with parenteral 5-azacytidine, and levels of embryonic globin RNA in circulating reticulocytes were measured. A very small but detectable amount of correctly initiated embryonic p-type globin RNA was detected in reticulocytes from birds treated with 5-azacytidine, while none was detected in reticulocytes from those receiving only phenylhydrazine or phenylhydrazine plus 1-beta-D-arabinofuranosylcytosine (cytosine arabinonucleoside). An attempt to increase embryonic globin RNA induction by treatment with parenteral sodium butyrate after 7 days of 5-azacytidine administration resulted in a 5- to 10-fold increase in the level of embryonic globin RNA. However, sodium butyrate did not induce embryonic gene expression when given alone or after treatment with cytosine arabinonucleoside. Sodium butyrate treatment also caused a DNase I-hypersensitive site to be exposed at the 5 end of the ...
Abstract Human β-globin disorders are relatively common genetic diseases cause by mutations in the β-globin gene. Increasing the expression of the γ-globin gene has great benefits in reducing complications associated with these diseases. The Oct-1 transcription factor is involved in the transcriptional regulation of the γ-globin gene. The human γ-globin genes (both Aγ and Gγ-globin genes) carry three Oct-1 transcription factor consensus sequences within their promoter regions. We have studied the possibility of inducing γ-globin gene expression using decoy oligonucleotides that target the Oct-1 transcription factor consensus sequence. A double-stranded 22 bp decoy oligonucleotide containing the Oct-1 consensus sequence was synthesized. The results obtained from our in vitro binding assay revealed a strong competitive binding of the decoy oligonucleotide for the Oct-1 transcription factor. When K562 human erythroleukemia cells were treated with the Oct-1 decoy oligonucleotide, significant
The globins are a superfamily of heme-containing globular proteins, involved in binding and/or transporting oxygen. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members include myoglobin and hemoglobin. Both of these proteins reversibly bind oxygen via a heme prosthetic group. They are widely distributed in many organisms. Globin superfamily members share a common three-dimensional fold. This globin fold typically consists of eight alpha helices, although some proteins have additional helix extensions at their termini. Since the globin fold contains only helices, it is classified as an all-alpha protein fold. The globin fold is found in its namesake globin families as well as in phycocyanins. The globin fold was thus the first protein fold discovered (myoglobin was the first protein whose structure was solved). The eight helices of the globin fold core share significant nonlocal structure, unlike other structural motifs in which amino ...
951 1234 DNase hypersensitive site 4 4550 4775 DNase hypersensitive site 3 8486 8860 DNase hypersensitive site 2 12752 13769 DNase hypersensitive site 1 116 431 Right Alu 1968 2258 Left Alu 5605 5918 Right Alu 8019 8314 Right Alu 10612 10924 Right Alu 12912 13066 Left L1 14836 15071 Right L1 16918 17218 Left Alu 17940 18231 Right Alu 19486 21080 epsilon-globin gene 19486 19632 Exon 1 19755 19977 Exon 2 20833 21080 Exon 3 23118 31136 Left L1 25885 27987 Left InnerL1 32407 32711 Right Alu 32986 33101 Left L1 34478 36069 G-gamma-globin gene 34478 34622 Exon 1 34745 34967 Exon 2 35854 36069 Exon 3 37921 38039 Left L1 39414 40985 A-gamma-globin gene 39414 39558 Exon 1 39681 39903 Exon 2 40770 40985 Exon 3 42695 43274 Left L1 44788 45108 Right Alu 45658 47272 eta-globin pseudo gene 45658 45800 Exon 1 45922 46144 Exon 2 46997 47272 Exon 3 50895 51198 Left Alu 51976 52276 Right Alu 53222 53540 Left L1 54740 56389 delta-globin gene 54740 54881 Exon 1 55010 55232 Exon 2 56131 56389 Exon 3 62137 63742 ...
Hemoglobin subunit epsilon is a protein that in humans is encoded by the HBE1 gene. The epsilon globin gene (HBE) is normally expressed in the embryonic yolk sac: two epsilon chains together with two zeta chains (an alpha-like globin) constitute the embryonic hemoglobin Hb Gower I; two epsilon chains together with two alpha chains form the embryonic Hb Gower II. Both of these embryonic hemoglobins are normally supplanted by fetal, and later, adult hemoglobin. The five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5 - epsilon - gamma-G - gamma-A - delta - beta - 3. Hemoglobin Human β-globin locus GRCh38: Ensembl release 89: ENSG00000213931 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000052217 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Higgs DR, Vickers MA, Wilkie AO, Pretorius IM, Jarman AP, Weatherall DJ (May 1989). A review of the molecular genetics of the human alpha-globin gene cluster. Blood. ...
TY - JOUR. T1 - Neuroglobin, a novel member of the globin family, is expressed in focal regions of the brain. AU - Mammen, Pradeep P A. AU - Shelton, John M.. AU - Goetsch, Sean C.. AU - Williams, S. Clay. AU - Richardson, James A.. AU - Garry, Mary G.. AU - Garry, Daniel J.. PY - 2002/12/1. Y1 - 2002/12/1. N2 - Hemoproteins are widely distributed among unicellular eukaryotes, plants, and animals. In addition to myoglobin and hemoglobin, a third hemoprotein, neuroglobin, has recently been isolated from vertebrate brain. Although the functional role of this novel member of the globin family remains unclear, neuroglobin contains a heme-binding domain and may participate in diverse processes such as oxygen transport, oxygen storage, nitric oxide detoxification, or modulation of terminal oxidase activity. In this study we utilized in situ hybridization (ISH) and RT-PCR analyses to examine the expression of neuroglobin in the normoxic and hypoxic murine brain. In the normoxic adult mouse, neuroglobin ...
A common mutation causing thalassemia in Mediterranean populations is an amber (UAG) nonsense mutation at the 39th codon of the human β globin gene, the β-39 mutation. Studies of mRNA metabolism in reticulocytes from patients with β-39 thalassemia and studies using heterologous transfection systems have suggested the possibility that this mutation affects not only protein synthesis but also alters mRNA metabolism. This phenomenon has been investigated further by two approaches. A careful series of RNA expression studies were performed comparing expression of β-39 to β-normal (β-nl). These experiments led to the conclusion that the defect in expression of the β-39 mRNA resides in the nucleus. A number of nonsense and missense mutations of the β globin gene were constructed by oligonucleotide-directed site-specific mutagenesis. Their expression was studied in a heterologous transfection system. These studies strongly suggest that the presence of a nonsense mutation (but not a missense mutation) in
Recent evidence suggests that long-range enhancers and gene promoters are in close proximity, which might reflect the formation of chromatin loops. Here, we examined the mechanism for DNA looping at the beta-globin locus. By using chromosome conformation capture (3C), we show that the hematopoietic transcription factor GATA-1 and its cofactor FOG-1 are required for the physical interaction between the beta-globin locus control region (LCR) and the beta-major globin promoter. Kinetic studies reveal that GATA-1-induced loop formation correlates with the onset of beta-globin transcription and occurs independently of new protein synthesis. GATA-1 occupies the beta-major globin promoter normally in fetal liver erythroblasts from mice lacking the LCR, suggesting that GATA-1 binding to the promoter and LCR are independent events that occur prior to loop formation. Together, these data demonstrate that GATA-1 and FOG-1 are essential anchors for a tissue-specific chromatin loop, providing general insights into
Highly purified RNase H (RNA·DNA hybrid ribonucleotidohydrolase, EC 3.1.4.34) from calf thymus was used to specifically remove the poly(A) sequences of purified rabbit globin mRNA after its hybridization with poly(dT). The deadenylylated globin mRNA was repurified by a one-step procedure including a nitrocellulose column. The poly(A) size and the content of unmodified mRNA were determined by hybridization with [(3)H]-poly(U), and it could be shown that the RNase H digestion method effectively removes this terminal poly(A) sequence. No difference in activity was found between mRNAs with and without poly(A) to initiate, elongate, terminate, and release newly synthesized globin chains in exogenous-mRNA-dependent, cell-free, protein-synthesizing systems from wheat embryo, ascites Krebs II cells, and rat liver. Furthermore, poly(A)-free globin mRNA competed with the same efficiency as authentic globin mRNA against chick ovalbumin mRNA when translated under total mRNA saturation conditions. It is ...
TY - JOUR. T1 - An erythroid chaperone that facilitates folding of α-globin subunits for hemoglobin synthesis. AU - Yu, Xiang. AU - Kong, Yi. AU - Dore, Louis C.. AU - Abdulmalik, Osheiza. AU - Katein, Anne M.. AU - Zhou, Suiping. AU - Choi, John K.. AU - Gell, David. AU - Mackay, Joel P.. AU - Gow, Andrew J.. AU - Weiss, Mitchell J.. PY - 2007/7/2. Y1 - 2007/7/2. N2 - Erythrocyte precursors produce abundant α- and β-globin proteins, which assemble with each other to form hemoglobin A (HbA), the major blood oxygen carrier. αHb-stabilizing protein (AHSP) binds free α subunits reversibly to maintain their structure and limit their ability to generate reactive oxygen species. Accordingly, loss of AHSP aggravates the toxicity of excessive free α-globin caused by β-globin gene disruption in mice. Surprisingly, we found that AHSP also has important functions when free α-globin is limited. Thus, compound mutants lacking both Ahsp and 1 of 4 α-globin genes (genotype Ahsp-/-α-globin -/-α/αα) ...
[Molecular mechanisms of globin gene regulation and disregulation].: Human globin genes are expressed in tissue and developmental stage specific manners. Variou
TY - JOUR. T1 - Characterization of an unique RNA initiated immediately upstream from human α1 globin gene in vivo and in vitro. T2 - Polymerase II-dependence, tissue specificity, and subcellular location. AU - Hess, John. AU - Perez-Stable, Carlos. AU - Deisseroth, Al. AU - Shen, Che Kun James. PY - 1985/9/11. Y1 - 1985/9/11. N2 - We have identified an abundant transcript initiated upstream from the canonical cap site of human α1 globin gene in bone marrow cells and in COS-7 cells transfected with an α1 globin gene-containing plasmid. Similar to the major α1 globin transcript, this upstream RNA is present almost exclusively in the cytoplasm of the transfected COS-7 cells. It is also synthesized efficiently in vitro by RNA polymerase II in the nuclear extracts prepared from a Hela cell line and an erythroleukemia cell line, K562. RNAs isolated from these cell lines, however, do not contain this upstream transcript. The putative 5′ end of the α1 globin upstream RNA is mapped by primer ...
The KLF1 gene encodes a key transcription factor regulating the developmental switch from fetal to adult globin. Based on previous and recent experimental data it has been hypothesized that after birth high levels of KLF1 activate the HBB gene and BCL11A expression, which in turn suppresses HBG1/HBG2 expression, while in the fetus reduced KLF1 levels result in very low HBB and BCL11A gene expression and therefore in low beta and high gamma globin levels.6 It is interesting to note that subjects II-1 and II-2, with genetic compound for the two KLF1 mutations, have unbalanced alpha/beta globin chain synthesis ratio (i.e. in the beta-thalassemia carrier range), despite having normal beta globin gene sequence and not increased HbA2 levels. The reduced beta globin production and the excess of G-gamma chains partly resembles a late fetal or newborn condition, consistent with the key role of KLF1 in the globin switching. The milder imbalance in II-2 as compared to II-1 is due to the coinheritance of ...
Expression patterns in the globin gene cluster are subject to developmental regulation in vivo. While the γA and γG genes are expressed in fetal liver, both are silenced in adult erythrocytes. In order to decipher the role of DNA methylation in this process, we generated a YAC transgenic mouse system that allowed us to control γA methylation during development. DNA methylation causes a 20-fold repression of γA both in non-erythroid and adult erythroid cells. In erythroid cells this modification works as a dominant mechanism to repress γ gene expression, probably through changes in histone acetylation that prevent the binding of erythroid transcription factors to the promoter. These studies demonstrate that DNA methylation serves as an elegant in vivo fine-tuning device for selecting appropriate genes in the globin locus. In addition, our findings provide a mechanism for understanding the high levels of γ-globin transcription seen in patients with Hereditary Persistence of Fetal Hemoglobin, and
Anthropogenetical Analysis of Abnormal Human -globin Gene Cluster Arrangement on Chromosome 16*. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Fetal hemoglobin, HbF (α2γ2), is the main hemoglobin synthesized up to birth, but it subsequently declines and adult hemoglobin, HbA (α2β2), becomes predominant. Several studies have indicated that expression of the HbF subunit γ-globin might be regulated post-transcriptionally. This could be confered by ~22-nucleotide long microRNAs that associate with argonaute proteins to specifically target γ-globin mRNAs and inhibit protein expression. Indeed, applying immunopurifications, we found that γ-globin mRNA was associated with argonaute 2 isolated from reticulocytes that contain low levels of HbF (,1%), whereas association was significantly lower in reticulocytes with high levels of HbF (90%). Comparing microRNA expression in reticulocytes from cord blood and adult blood, we identified several miRNAs that were preferentially expressed in adults, among them miRNA-96. The overexpression of microRNA-96 in human ex vivo erythropoiesis decreased γ-globin expression by 50%, whereas the ...
We introduced into MEL cells rabbit beta-globin gene deletion mutants and two sets of hybrid genes constructed from the inducible human beta-globin gene and noninducible human gamma-globin gene or the murine H-2Kbm1 class I MHC gene. S1 nuclease analysis of gene transcripts before and after MEL diff …
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TY - JOUR. T1 - Hpal polymorphic site 3 of the human β-globin gene is inside a repetitive sequence and cannot be ascertained by polymerase chain reaction. AU - Wang, X.. AU - Bouhassira, Eric E.. PY - 1992. Y1 - 1992. KW - Haplotype. KW - Kpnl sequence. KW - PCR. UR - http://www.scopus.com/inward/record.url?scp=0026603960&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0026603960&partnerID=8YFLogxK. M3 - Article. VL - 39. SP - 226. EP - 227. JO - American Journal of Hematology. JF - American Journal of Hematology. SN - 0361-8609. IS - 3. ER - ...
The apparent stasis in the evolution of avian chromosomes suggests that birds may have experienced relatively low rates of gene gain and loss in multigene families. To investigate this possibility and to explore the phenotypic consequences of variation in gene copy number, we examined evolutionary changes in the families of genes that encode the α- and β-type subunits of hemoglobin (Hb), the tetrameric α2β2 protein responsible for blood-O2 transport. A comparative genomic analysis of 52 bird species revealed that the size and membership composition of the α- and β-globin gene families have remained remarkably constant during approximately 100 My of avian evolution. Most interspecific variation in gene content is attributable to multiple independent inactivations of the αD-globin gene, which encodes the α-chain subunit of a functionally distinct Hb isoform (HbD) that is expressed in both embryonic and definitive erythrocytes. Due to consistent differences in O2-binding properties between HbD and
Androglobin (Adgb) is a recently discovered globin type consisting of large chimeric proteins with an N-terminal calpain-like protease domain and a central globin domain. Adgb is predominantly expressed in testis tissue and the expression is associated with the post-meiotic stages of spermatogenesis. Although we knew that Adgb plays a crucial role in male fertility, its molecular function is still not clear. The aim of this thesis was clear: unraveling the molecular function of Adgb. This was approached by using different strategies: the function was studied on biochemical, cellular and biological level.. To perform an in vitro biochemical characterization of the globin domain of Adgb, the globin domain was recombinantly expressed in E.coli, P.pastoris and baculovirus infected insect cells. We encountered difficulties with the solubility of the globin domain and concluded that for a proper folding it requires the context of the full length Adgb protein. Hence, we expressed the full length Adgb ...
In the vascular wall, endothelial nitric oxide synthase (eNOS) produces NO to regulate peripheral vascular resistance, tissue perfusion, and blood pressure. In resistance arteries, eNOS couples with α-globin and, through chemical reactions, modulates NO diffusion needed for vascular smooth muscle relaxation. While α-globin protein alone is known to be unstable, the mechanisms that enable α-globin protein expression remain elusive. Here, Lechauve et al. report that arterial endothelium expresses α hemoglobin-stabilizing protein, which acts as a critical chaperone protein for α-globin expression and vascular function.. ...
We have constructed a minilocus that contains the 5 and 3 flanking regions of the human beta-globin locus and the beta-globin gene. These regions are characterized by erythroid-specific DNAase I-superhypersensitive sites and are normally located approximately 50 kb 5 and 20 kb 3 of the beta-gl …
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
GLOBINclear-Human Globin mRNA Removal Kit Depletes alpha and beta globin mRNA from blood total RNA with a simple magnetic bead procedure (no enzymatic treatments) Increases sensitivity of gene detection in microarray profiling experiments ,Unmask,Blood,RNA,for,Gene,Expression,Profiling,biological,advanced biology technology,biology laboratory technology,biology device technology,latest biology technology
Takaras Human Beta-globin Control Primer Set contains a set of PCR primers that recognizes the human beta-globin gene at chromosome 11. Beta-globin makes up about half of the human hemoglobin tertrameric protein; in the normal human adult, the hemoglobin tetramer consists of two alpha chains and two beta chains. The Human Beta-globin Control Primer Set may be used as a experimental control during protocols such as PCR ...
The work in our laboratory focuses on analyzing the regulation of globin gene expression in red blood cells. The globin genes encode for components of hemoglobin. We use a combination of genetic and biochemical approaches to analyze the structure and function of the human b-globin locus control region (LCR), a powerful regulatory genetic element located far upstream of the globin genes. The LCR, which is composed of several sub-regions revealing high sensitivity to nucleases in erythroid cells enhances globin gene transcription in a developmental stage specific manner. We use transgenic mice, embryonic stem (ES) cell differentiation systems, and in vitro assays to elucidate the mechanism by which the LCR regulates the recruitment of transcription and chromatin modifying complexes to the b-globin gene locus.. ...
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In the post-genomic era, a great deal of work has focused on understanding how DNA sequence is used to programme complex nuclear, cellular and tissue functions throughout differentiation and development. There are many approaches to these issues, but we have concentrated on understanding how a single mammalian gene cluster is activated or silenced as stem cells undergo lineage commitment, differentiation and maturation. In particular we have analysed the alpha globin cluster, which is expressed in a cell-type- and developmental stage-specific manner in the haemopoietic system. Our studies include analysis of the transcriptional programme that accompanies globin gene activation, focusing on the expression of relevant transcription factors and cofactors. Binding of these factors to the chromosomal domain containing the alpha globin cluster has been characterized by ChIP (chromatin immunoprecipitation). In addition, we have monitored the epigenetic modifications (e.g. nuclear position, timing of
The β‐globin constructs with the wild‐type ORF or with the nonsense codon at position 39 (NS 39) contain a genomic 1423 bp β‐globin gene fragment extending from the physiological translation initiation codon to the translation termination codon, which was inserted into the pCIneo vector (Promega) at the XhoI-XbaI sites of the polylinker. The wild‐type and NS 39 gene sequences were derived from a healthy proband and from a patient with homozygous β‐thalassaemia, respectively. Constructs cWT and cNS 39 were derived from RT-PCRs of cytoplasmic RNA from HeLa cells transfected with wild‐type and NS 39 constructs and were inserted into the same position of the pCIneo vector.. The cWT‐UTR and the cNS 39‐UTR series of constructs was generated by replacement of a fragment spanning from the EcoRI site in the nominal exon 3 to an XhoI site that was inserted by in vitro mutagenesis immediately 3′ of the termination codon by sequences extending from the same EcoRI site to the XhoI site ...
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Thalassemic syndromes are genetically determined disorders of hemoglobin synthesis with decreased production of either alpha or beta polypeptide chains of hemoglobin molecules. This reduced production results from markedly decreased amounts of globin messenger ribonucleic acid.
Generation of mice deficient in both KLF3/BKLF and KLF8 reveals a genetic interaction and a role for these factors in embryonic globin gene silencing. Alister P. W. Funnel, Ka Sin Mak, Natalie A. Twine, Gregory J. Pelka, Laura J. Norton, Tania Radziewic, Melinda Power, Marc R. Wilkins, Kim S. Bell-Anderson, Stuart T. Fraser, Andrew C. Perkins, Patrick P. Tam, Richard C. M. Pearson and Merlin Crossley. Mol Cel Biol. (2013) Aug; 33(15):2976-87. IF=4.2 Cit=15 (GS 18) ...
Preparations comprising, especially, globin that is insoluble at neutral pH, and therefore at physiological pH, in which the globin has been obtained from whole blood by depigmentation in a medium tha
The globin gene superfamily as a model system. A second area of research is geared towards understanding the role of gene duplication and whole-genome duplication in the evolution of key physiological innovations. Gene duplication is thought to play an extremely important role in the evolution of novel protein and pathway functions. However, there is still much debate about the specific evolutionary mechanisms that are responsible for the initial retention and subsequent functional divergence of duplicated genes. The globin gene superfamily is an ideal model system for investigating these issues because it is one of the most intensively studied multigene families from the standpoint of molecular genetics and phylogenetic history. The globin gene families also provide an excellent example of the kind of physiological versatility that can be attained through functional and regulatory divergence of duplicated genes that encode different subunit polypeptides of the same multimeric protein. For ...
Four polypeptide globin chains are arranged in pairs forming the tetrameric molecule or globin portion of hemoglobin. Each globin chain is covalently attached to a heme moiety.. The globin tetramer is globular or ellipsoid in shape, being approximately 550nm in diameter. The four porphyrin heme moieties lie in four regularly spaced clefts on the tetramer surface.. The globin portion of most normal hemoglobins consists of two chains from chromosome 16 and two from chromosome 11. Normal a chains contain 141 amino acids; normal ß chains 146 amino acids. The d chain varies by 10 aa; the g chain by 39 aa compared with the ß chain ...
Annotated images of multiple alignments: HSs in the mammalian beta-globin LCR How to contact us NOTE: These pages are under constant revision, and are located on several physical systems. Please be careful to only bookmark our published URL, http://www.bx.psu.edu/, otherwise your links to internal pages may go stale. ...
Xenopus embryos contain a considerable amount of a polysialo-ganglioside not yet fully characterized; in this paper, we will refer to it as ganglioside XI. Preliminary experiments indicate asialo-GMI as the core structure of the ganglioside XI and pa
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
A team of scientists at the University of California, Davis, and the University of Auckland has discovered that neuroglobin may protect against Alzheimers disease by preventing brain neurons from dying in response to natural stress. A team of scientists at the University of California, Davis and the University of Auckland has discovered that neuroglobin may protect against Alzheimers disease by preventing brain neurons from dying in response to natural stress. The team published the results of their study in the April, 2010 issue of Apoptosis.. Scientists have learned that neuroglobin protects cells from stroke damage, amyloid toxicity and injury due to lack of oxygen. Neuroglobin occurs in various regions of the brain and at particularly high levels in brain cells called neurons. Scientists have associated low levels of neuroglobin in brain neurons with increased risk of Alzheimers disease. Recent studies have hinted that neuroglobin protects cells by maintaining the function of mitochondria ...
In 2015, a group of Chinese researchers repo--rted replacing a mutated gene that encodes the β-globin protein, a gene responsible for the development of β-thalassemia, in pre-implantation human embryos.1 While only 4 of the 86 embryos contained the replaced DNA, this discovery heralded the possibility of removing mutations and making epigenetic changes to the genome that could protect humans from diseases. It also adds a new level of complexity to decisions regarding changing the fate of future generations, a question that haunts many parents and policy workers today. With this advancement, expectant parents may have the ability to protect their children from certain diseases while also introducing them to novel, unanticipated ailments. Such advancement could thus blur the boundary between disease prevention and acceptance of genetic diversity. My father once told me the story of how a deaf girl grew up to become a professional clarinet player. Because of a recessive mutation, she had to learn ...
An example of a complex eukaryotic KOG: globins and related hemoproteins. The systematic protein names of the KOG members are listed under each species. To the
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Impaired switching from fetal hemoglobin (HbF) to adult globin gene expression leads to hereditary persistence of fetal hemoglobin (HPFH) in adult life. This is of prime interest because elevated HbF levels ameliorate beta-thalassemia and sickle cell anemia. Fetal hemoglobin levels are regulated by complex mechanisms involving factors linked or not to the beta-globin gene locus. To search for factors putatively involved in gamma-globin gene expression, we examined the reticulocyte transcriptome of three siblings who had different HbF levels and different degrees of beta-thalassemia severity although they had the same alpha- and beta-globin gene cluster genotypes. Using a differential mRNA display approach, we identified a cDNA of the cold shock domain protein A (CSDA), a trans-acting factor previously reported to interact in vitro with the gamma-globin gene promoter. Real time quantitative analysis in the three patients and CSDA expression studies in the human erythroleukemic K562 cell line ...
Fetuses with homozygous α-thalassemia usually die at the third trimester of pregnancy or soon after birth. Hence, the disease could potentially be a target for fetal gene therapy. We have previously established a mouse model of α-thalassemia. These mice mimic the human -thalassemic conditions and can be used as preclinical models for fetal gene therapy. We tested a lentiviral vector containing the HS 2, 3, and 4 of the -LCR, a central polypurine tract element, and the -globin gene promoter directing either the EGFP or the human -globin gene. We showed that the GFP expression was erythroid-specific and detected in BFU-E colonies and the erythroid progenies of CFU-GEMM. For in utero gene delivery, we did yolk sac vessel injection at midgestation of mouse embryos. The recipient mice were analyzed after birth for human -globin gene expression. In the newborn, human -globin gene expression was detected in the liver, spleen, and peripheral blood. The human -globin gene expression was at the peak at ...
Background: Eukaryotic cells have developed surveillance mechanisms to prevent the expression of aberrant transcripts. An early surveillance checkpoint acts at the transcription site and prevents the release of mRNAs that carry processing defects. The exosome subunit Rrp6 is required for this checkpoint in Saccharomyces cerevisiae, but it is not known whether Rrp6 also plays a role in mRNA surveillance in higher eukaryotes.. Methodology/Principal Findings: We have developed an in vivo system to study nuclear mRNA surveillance in Drosophila melanogaster. We have produced S2 cells that express a human β-globin gene with mutated splice sites in intron 2 (mut β-globin). The transcripts encoded by the mut β-globin gene are normally spliced at intron 1 but retain intron 2. The levels of the mut β-globin transcripts are much lower than those of wild type (wt) ß-globin mRNAs transcribed from the same promoter. We have compared the expression of the mut and wt β-globin genes to investigate the ...
Four distinct factors in extracts from murine erythroleukemia (MEL) cells interacted with the human beta-globin gene promoter CAAT box: CP1, GATA-1, and two novel factors, denoted a and b, one of which is highly inducible in the MEL system. GATA-1 binding to the CAAT element was very unstable (half-life | 1 min), whereas bindings of a, b, and CP1 were comparatively stable, with half-lives of 18, 19, and 3.5 min, respectively. Stable transfections of MEL cells showed that in the presence of the beta-globin locus control region (LCR), the wild-type CAAT box, a mutant which bound to GATA-1 with increased stability over the normal sequences, and a mutant which bound a, b, and CP1 specifically could all stimulate transcription greater than ninefold over that induced by a null CAAT mutation in both uninduced and terminally differentiated MEL cells. A mutant which bound the a and b factors specifically gave only a twofold stimulation of promoter activity, and this lower activity correlated with a decrease in
Over 7% of the global population are carriers of haemoglobinopathies. However, despite their prevalence, no effective treatments exist for β-thalassemia and sickle-cell anaemia beyond lifelong blood transfusions. The globin genes are expressed sequentially during development and nature has an inbuilt compensation mechanism when the adult β-globin gene has been deleted: the reactivation of fetal γ-globin, resulting in the benign condition hereditary persistence of fetal haemoglobin. The amelioration of the symptoms of β-globinopathies in the rare cases where these disorders are co-inherited has inspired decades of research into the molecular regulation of haemoglobin switching, with the aim of inducing therapeutic γ-globin expression. In spite of this, the mechanism remains unsolved, partly due to the lack of suitable cell and animal models available. Our lab has developed a novel system for studying and manipulating haemoglobin switching in vitro. We have generated mouse embryonic stem cell ...
Nature 406, 82 - 86 (2000) © Macmillan Publishers Ltd. Therapeutic haemoglobin synthesis in -thalassaemic mice expressing lentivirus-encoded human -globin CHAD MAY, STEFANO RIVELLA, JOHN CALLEGARI, GLENN HELLER, KAREN M. L. GAENSLER, LUCIO LUZZATTO & MICHEL SADELAIN The stable introduction of a functional -globin gene in haematopoietic stem cells could be a powerful approach to treat -thalassaemia and sickle-cell disease. Genetic approaches aiming to increase normal -globin expression in the progeny of autologous haematopoietic stem cells might circumvent the limitations and risks of allogeneic cell transplants. However, low-level expression, position effects and transcriptional silencing hampered the effectiveness of viral transduction of the human -globin gene when it was linked to minimal regulatory sequences. Here we show that the use of recombinant lentiviruses enables efficient transfer and faithful integration of the human -globin gene together with large segments of its locus control ...
The oxygen-transport function of hemoglobin (HB) is thought to have arisen ~500 million years ago, roughly coinciding with the divergence between jawless (Agnatha) and jawed (Gnathostomata) vertebrates. Intriguingly, extant HBs of jawless and jawed vertebrates were shown to have evolved twice, and independently, from different ancestral globin proteins. This raises the question whether erythroid-specific expression of HB also evolved twice independently. In all jawed vertebrates studied to date, one of the Hb gene clusters is linked to the widely expressed Nprl3 gene. Here we show that the nprl3-linked hb locus of a jawless vertebrate, the river lamprey (Lampetra fluviatilis), shares a range of structural and functional properties with the equivalent jawed vertebrate Hb locus. Functional analysis demonstrates that an erythroid-specific enhancer is located in intron 7 of lamprey nprl3, which corresponds to the NPRL3 intron 7 MCS-R1 enhancer of jawed vertebrates. Collectively, our findings signify ...
Gene therapy could represent an alternative to hematopoietic stem cell transplantation (HCT) - the only curative therapy for beta-thalassemia - and may offer several advantages over HCT, including tailored conditioning with no need for immunosuppression after gene therapy and no risk of graft-versus-host disease or rejection. According to results from a phase I/II trial presented at the 2017 ASH Annual Meeting, patients with transfusion-dependent beta-thalassemia had a significantly reduced need for blood transfusions after receiving a single infusion of cells carrying corrected genes.. Sarah Marktel, MD, of the Hematology and BMT Unit IRCCS San Raffaele Scientific Institute in Milan, Italy, explained during her presentation that the investigational gene therapy protocol used in this trial was based on the high-titer vector GLOBE, a third-generation self-inactivating lentiviral vector encoding for the human beta globin gene.. In the TIGET-BTHAL trial, patients with beta-thalassemia of any ...
TY - JOUR. T1 - HS2 enhancer function is blocked by a transcriptional terminator inserted between the enhancer and the promoter. AU - Ling, Jianhua. AU - Ainol, Lincoyan. AU - Zhang, Ling. AU - Yu, Xiuping. AU - Pi, Wenhu. AU - Tuan Lo, Dorothy. PY - 2004/12/3. Y1 - 2004/12/3. N2 - The HS2 enhancer in the β-globin locus control region regulates transcription of the globin genes 10-50 kb away. How the HS2 enhancer acts over this distance is not clearly understood. Earlier studies show that in erythroid cells the HS2 enhancer initiates synthesis of intergenic RNAs from sites within and downstream of the enhancer, and the enhancer-initiated RNAs are transcribed through the intervening DNA into the cis-linked promoter and gene. To investigate the functional significance of the enhancer-initiated transcription, here we inserted the lac operator sequence in the intervening DNA between the HS2 enhancer and the eglobin promoter in reporter plasmids and integrated the plasmids into erythroid K562 cells ...
Analysis of DNA from 852 Island Melanesians has revealed a high frequency of single- and triple-gamma-globin genes in this population. Homozygotes for triple- and single-gamma genes have normal hematologic findings, normal hemoglobin F (HbF) levels, and when there is coexisting alpha thalassemia, appropriate levels of Barts Hb (gamma 4) at birth. In addition, we have identified an individual with a quadruple-gamma gene chromosome who also has a normal HbF level. All single-gamma genes were A gamma, all triple-gamma genes G gamma G gamma A gamma, and the quadruple-gamma gene G gamma G gamma G gamma A gamma. Analysis of G gamma:A gamma ratios in cord bloods and HbF levels in adults showed that these additional gamma genes are expressed and are down regulated appropriately by the fetal to adult Hb switch. Analysis of the restriction enzyme haplotypes of these various chromosomes indicates that intrachromosomal cross-overs are more likely to have produced these variants than interchromosomal recombination
TY - JOUR. T1 - Severe Hb S-β°-thalassaemia with a T→C substitution in the donor splice site of the first intron of the β-globin gene. AU - Gonzalez-Redondo, J. M.. AU - Stoming, T. A.. AU - Kutlar, Ferdane. AU - Kutlar, Abdullah. AU - McKie, V. C.. AU - McKie, K. M.. AU - Huisman, T. H.J.. PY - 1989/1/1. Y1 - 1989/1/1. N2 - Through direct sequencing and dot-blot analyses with synthetic oligonucleotide probes of amplified DNA, a new nucleotide substitution was discovered in a Black teenager with severe Hb S-β°-thalassaemia. The substitution involved a T→C replacement at the second position of the donor splice site of the first intervening sequence of the β-globin gene. The clinical and haematological observations made in Black subjects with Hb S-β°-thalassaemia, with different types of thalassaemia, suggest severe disease resembling sickle cell anaemia. Only an occasional patient had a milder clinical course, perhaps because of a greatly increased production of fetal ...
Animal models of β-hemoglobinopathies: utility and limitations Bradley McColl, Jim Vadolas Cell and Gene Therapy Laboratory, Murdoch Childrens Research Institute, Royal Childrens Hospital, Parkville, VIC, Australia Abstract: The structural and functional conservation of hemoglobin throughout mammals has made the laboratory mouse an exceptionally useful organism in which to study both the protein and the individual globin genes. Early researchers looked to the globin genes as an excellent model in which to examine gene regulation - bountifully expressed and displaying a remarkably consistent pattern of developmental activation and silencing. In parallel with the growth of research into expression of the globin genes, mutations within the β-globin gene were identified as the cause of the β-hemoglobinopathies such as sickle cell disease and β-thalassemia. These lines of enquiry stimulated the development of transgenic mouse models, first carrying individual human globin genes and then substantial
Supplementary Components1. disease (SCD) will be the most common monogenic illnesses.1,2 Both disorders could Salinomycin inhibition be ameliorated by increased degrees of fetal hemoglobin (HbF).3C5 In -thalassemia, where -globin expression is decreased or absent, -globin production can bring back normal globin chain assembly into functional hemoglobin.5 In SCD, the substitution of glutamic acid for valine in the sixth amino acid from the -globin protein qualified prospects to the forming of abnormal hemoglobin S (HbS).6 Pursuing deoxygenation in red bloodstream cells (RBCs), HbS forms polymers leading to the Salinomycin inhibition RBCs to be deformed and adherent resulting in vaso-occlusive events leading to splenic infarction, kidney failure, heart stroke, painful crises, and chronic anemia. research have shown how the HbF (22) tetramer as well as Salinomycin inhibition the (2S) tetramer inhibit HbS polymerization.7,8 Induction of fetal hemoglobin can be an important therapeutic strategy in ...
A-globin locus mRNA expression (alpha-, mu-, theta-, zeta-, globin) shown in Figure 1B demonstrated no significant Gracillin changes in mRNA levels compared to
Epigenetic regulation of gene expression is a developing field of study with many potential therapeutic applications. Chromatin remodeling is necessary for proper mammalian development, and misregulation of this process is associated with many human diseases. Three mechanisms by which chromatin structure is modified include methylation of the DNA, covalent modification of histone tails, and repositioning of nucleosomes by ATP dependant chromatin remodeling enzymes. To further increase our knowledge of the mechanisms and proteins involved in the modification of chromatin structure I undertook two projects; the role of DNA methylation in the regulation of human β-globin gene expression, and analysis of the Chd6 ATPase-/- mouse. Methylation status of the human β-globin gene promoters correlates with the expression pattern of the individual genes. However an extensive locus wide analysis of the methylation pattern in primary human tissue has not been performed. We used bisulfite sequencing to ...
Epigenetic regulation of gene expression is a developing field of study with many potential therapeutic applications. Chromatin remodeling is necessary for proper mammalian development, and misregulation of this process is associated with many human diseases. Three mechanisms by which chromatin structure is modified include methylation of the DNA, covalent modification of histone tails, and repositioning of nucleosomes by ATP dependant chromatin remodeling enzymes. To further increase our knowledge of the mechanisms and proteins involved in the modification of chromatin structure I undertook two projects; the role of DNA methylation in the regulation of human β-globin gene expression, and analysis of the Chd6 ATPase-/- mouse. Methylation status of the human β-globin gene promoters correlates with the expression pattern of the individual genes. However an extensive locus wide analysis of the methylation pattern in primary human tissue has not been performed. We used bisulfite sequencing to ...
We have found that the major globin gene locus of zebrafish (Danio rerio) is structurally and functionally segregated into two spatially distinct subloci harboring either adult or embryo-larval globin genes, said Razin. These subloci demonstrate different organization at the level of chromatin domains and different modes of spatial organization, which appears to be due to selective interaction of the upstream gene enhancer with the sublocus harboring globin genes of the adult type ...
Miller, D M.; Turner, P; Nienhuis, A W.; Axelrod, D E.; and Gopalakrishnan, T V., Active conformation of the globin genes in uninduced and induced mouse erythroleukemia cells. (1978). Subject Strain Bibliography 1978. 3642 ...
The β-globin gene is a member of a family located on chromosome 11. As in the α-globin gene family, epsilon (∊), the most 5′ (upstream) of these genes, is expressed only in early embryos. Downstream from this gene are two tandem gamma (γ) genes whose product is found in fetal hemoglobin (Hb F, α2β2), the hemoglobin that predominates throughout most of gestation. The delta (δ) gene product forms a minor hemoglobin component, Hb A2 (α2β;2), which has no functional importance but is useful in the diagnosis of the thalassemias (discussed later in this chapter.) The most 3′ (downstream) member of the family is the β gene whose product combines with α-globin to form Hb A (α2β2), the major hemoglobin component of adult red cells. ...
During physiological aerobic metabolism, the epidermis undergoes significant oxidative stress as a result of the production of reactive oxygen species (ROS). To maintain a balanced oxidative state, cells have developed protective antioxidant systems, and preliminary studies suggest that the transcriptional factor p63 is involved in cellular oxidative defence. Supporting this hypothesis, the ΔNp63α isoform of p63 is expressed at high levels in the proliferative basal layer of the epidermis. Here we identify the CYGB gene as a novel transcriptional target of ΔNp63 that is involved in maintaining epidermal oxidative defence. The CYGB gene encodes cytoglobin, a member of the globin protein family, which facilitates the diffusion of oxygen through tissues and acts as a scavenger for nitric oxide or other ROS. By performing promoter activity assays and chromatin immunoprecipitation, reverse transcriptase quantitative PCR and western blotting analyses, we confirm the direct regulation of CYGB by ΔNp63α.
beta-Globins: Members of the beta-globin family. In humans, they are encoded in a gene cluster on CHROMOSOME 11. They include epsilon-globin, gamma-globin, delta-globin and beta-globin. There is also a pseudogene of beta (theta-beta) in the gene cluster. Adult HEMOGLOBIN is comprised of two ALPHA-GLOBIN chains and two beta-globin chains.
Abstract. Mutations within exon 3 of the beta-globin gene are relatively uncommon, and many of these mutations produce a dominant thalassemia- like phenotype.
Most of the α-thalassemias are caused by deletions that remove one or more of the α-globin gene loci. The severity of the disease that results from these lesions is directly proportional to the number of α-globin genes that are missing ...
Evidence-Based Complementary and Alternative Medicine (eCAM) is an international peer-reviewed, Open Access journal that seeks to understand the sources and to encourage rigorous research in this new, yet ancient world of complementary and alternative medicine.
In our two papers (1, 2) in which we have detailed the factual basis and theoretical implications of molecular drive, we have defined it as a process of fixing a mutation within multigene and non-genic families in a population, as a consequence of DNA turnover. Considerations of rates of turnover indicate that individuals of a sexual population would change in unison with respect to the changing composition of a family. At the heart of molecular drive is the widespread phenomenon of concerted evolution. Although the reality of this phenomenon is incontestable, we cannot accept the definitive statement of Lewins, drawing in particular on remarks made by A. Jeffreys on the human globin cluster and Alu family, that it is not a universal phenomenon. Concerted evolution is occurring in the globin cluster; indeed this phenomenon was first defined as such in this cluster due to the homogenization of pairs of [alpha] and [gamma] genes, and their flanking sequences, by unequal exchange or gene ...
α-globin-like genes on chromosome 16 β-globin-like genes on chromosome α-Gene family: contains a- two genes for the α-globin chains b-The ζ-gene which is expressed. c- other globin-like genes that are not expressed (pseudogenes). α-globin-like genes on chromosome 16 β-globin-like genes on chromosome α-Gene family: contains a- two genes for the α-globin chains b-The ζ-gene which is expressed. c- other globin-like genes that are not expressed (pseudogenes). Organization of the globin genes
Following cleaning with detergent and water at the end of the working day (sampling 1), nine of the 20 surfaces tested were contaminated. It was decided to clean surfaces with a more stringent agent. After subsequent cleaning with Clearsol solution HPV DNA was present on one surface at the beginning of the day, and on four at the end of the day.. β Globin DNA was detected in all HPV DNA positive samples, indicating HPV was cell associated, and in a further five samples taken at the end of the day from HPV DNA negative surfaces.. Compared to our previous study a 50% reduction in surface contamination with HPV DNA was found after cleaning with detergent and the number of types detected was reduced. Only HPV types 6, 11, 16, and 58 were detected on the nine different surfaces. This is also a 73% reduction in the number of types detected in our previous study.1 HPV types 6, 11, and 16 were still the most common types found (all types in table 1).. Three of the samples positive for β globin DNA but ...
Meythlation is extremely important when it comes to gene expression. not all genes are active at all times which is why DNA methylation is one of the several mechanics that allow cells to control gene expression. Although there are many ways that a gene can be expressed in particularly eukaryotes, the methylation of DNA is a common epigenetic signaling tool that can allow cells to lock genes in the off position. Key experiments were needed in order to provide the early clues for what the role of methylation had on gene expression. One such experiment was conducted by McGhee and Ginder in 1979 where they compared the methylation status of beta-globin loci in cells that did and that did not express the gene. By utilizing restriction enzymes that distinguished between methylated and unmethylatd DNA, the two scientists were capable of dictating that the beta globin locus gene was not being expressed in the cells that were unmethylated. In addition to this experiment, more supporting evidence ...
摘要 构建重组表达载体是转基因动物生产制备研究中非常关键的一步,包括构建完整的外源基因表达盒,包含目的基因、调控序列(启动子、终止子)和筛选报告基因等。本文概述了转基因大动物制备技术,归纳统计了近10年转基因猪、牛、羊制备过程中常用的载体和频数,统计结果表明,转基因猪中启动子频数从多到少依次为酪蛋白、CAG、CMV启动子,终止子频数依次为兔β-globin poly A、酪蛋白poly A、SV40 poly A和BGH poly A;转基因羊中启动子频数从多到少依次为酪蛋白、BLG和CMV启动子,终止子依次为酪蛋白poly A、BLG poly A、BGH poly A、SV40 poly A和兔β-globin poly A;转基因牛中启动子频数从多到少依次为酪蛋白、CMV、人乳清白蛋白启动子等,终止子依次为SV40 poly A、BGH poly A和酪蛋白poly ...
red blood cells, to help maintain energy levels, health and vitality.. The GHL Advantage - Critical for Healthy Blood. Glycine: Essential for the formation of haem which carries the iron and oxygen in the red blood cell.. Histidine: Helps to manufacture red and white blood cells. Red blood cells are oxygen-carrying cells. White blood cells are part of our immune system. They protect our body from harmful microorganisms (infection).. Lysine: Essential to the formation of proteins like the globin protein found in haemoglobin. Deficiency results in tiredness, dizziness and anemia.. ...
Myoglobin, molecular model. Myoglobin is a protein found in muscle tissue, where it binds to and stores oxygen to be used during strenuous exercise. The structure of the globin protein protects the haem (iron) group from being oxidised and destroyed by the oxygen it carries. - Stock Image F009/6153
Myoglobin, molecular model. Myoglobin is a protein found in muscle tissue, where it binds to and stores oxygen to be used during strenuous exercise. The structure of the globin protein protects the haem (iron) group from being oxidised and destroyed by the oxygen it carries. - Stock Image F006/9417
Generation of mutant mice. In the strategy of IMCT (Kobayashi et al., 1995), transgenic (Tg) mice are generated that express the human interleukin-2 receptor α-subunit (IL-2Rα) under the control of a cell type-specific promoter. These mice are then treated with a recombinant immunotoxin (IT), which is composed of the variable regions of the anti-IL-2Rα monoclonal antibody and a bacterial exotoxin fragment. The transgene construct contained a 10 kb DNA fragment encoding the 5′-flanking region of the mouse neuropsin (NP) gene (Hirata et al., 2001), the second intron of the rabbit β-globin gene (Kobayashi et al., 1992), the gene cassette encoding IL-2Rα fused to green fluorescent protein (IL-2Rα/GFP) (Watanabe et al., 1998), and the polyadenylation signals of the rabbit β-globin gene and simian virus 40 early gene (Kobayashi et al., 1992). The construct was microinjected into fertilized mouse eggs, which were then implanted into pseudopregnant females. Tg mice were identified by Southern ...
Fetal Hemoglobin Lysate, 0.1 mg. The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow.
Journal of Clinical and Diagnostic Research aims to publish findings of doctors at grass root level and post graduate students, so that all unique medical experiences are recorded in literature.
human beta-globin gene inhibits pre-mRNA splicing: a mechanism for beta+-thalassemia. Proc. Natl. Acad. Sci. U.S.A. 86 (3): 1041-5. doi:10.1073/pnas. ...
HEMOGLOBINOPATHIES. BIOCHEMISTRY DR AMINA TARIQ. A large number of mutations have been described in the globin genes. These mutations can be divided into two distinct types: Slideshow 2129166 by jory
β-Talasemi Azerbaycan da g r len en s k kal tsal hastal kt r. al mam z n amac Azerbaycan pop lasyonunda en s k g r len β-talasemi mutasyonlar n n genotip-fenotip korelasyonlar n n ortaya kar lmas yd . Yerel pop lasyonda en s k g r len β-globin gen mutasyonlar olan kodon 8 (-AA), IVS-I-6 (T>C) ve IVS-II-1 (G>A) mutasyonlar n ta yan hastalar hematolojik parametreler a s ndan de erlendirildi. Daha nceden test edilmi ve genotipik zellikleri bilinen 55 hasta al maya dahil edildi. Mutasyonlar n fenotipik manifestasyonlar n n g sterilmesi i in hematolojik indeksler ve hemoglobin fraksiyonlar na bak ld . Sonu lar farkl β-globin gen mutasyonlar aras nda klinik ba vuru a s ndan farkl l klar oldu unu g stermekteydi: IVS-I-6 (T>C) mutasyonu olan bireylerde hastal k kodon 8 (-AA) ve IVS-II-1 (G>A) mutasyonu olanlara g re daha hafif seyretmekteydi. Erken genotipik tan mlama klinik ba vuru zelliklerinin tahmin edilmesine ve hastalara en iyi terap tik yakla mlar n uygulanmas na yard mc olabilir ...
The AG promoter sequence consists of the chicken β-actin promoter, the first exon and part of the first intron (that seems to have a strong enhancer-like activity) linked to a rabbit β-globin fragment, consisting of a 3 part of the second intron (inclusive a branch point which is required for normal splicing reactions) and a 5 part of the third exon ...
The AG promoter sequence consists of the chicken β-actin promoter, the first exon and part of the first intron (that seems to have a strong enhancer-like activity) linked to a rabbit β-globin fragment, consisting of a 3 part of the second intron (inclusive a branch point which is required for normal splicing reactions) and a 5 part of the third exon ...
The grey zone demarcates the vary within which 95% of non-sickle mobile ailment red cells fall, as well as the black curve will be the indicate curve for nutritious contributors. The elongation index was calculated since the ratio in the duration (A) and width (B) of a mobile, where (A−B) was divided by (A+B), and the result was expressed like a decimal concerning 0 and one. Panel E exhibits the crimson-mobile density profile 12 months soon after gene therapy during the affected individual, attained with the use of a phthalate gradient. We measured 10 samples (indicated with the figures one by means of ten over the black curve) at a variety of phthalate densities. Purple strains demarcate a few unique densities of cells: lower (one.096 mg for every milliliter). Orange lines suggest restrictions of a traditional profile. The values for that affected person are shifted for the remaining as a result of linked one α-globin gene deletion. Cells denser than one.one hundred ten mg per milliliter of ...
In utero delivery of nanoparticles containing peptide nucleic acids (PNAs) and donor DNAs in fetal mouse tissues to correct a disease-causing mutation in the β-globin gene in a mouse model of human β- ...
Svět potřebuje vědu, věda potřebuje ženy. Právě proto mají české vědkyně už podvanácté možnost získat ocenění ve výši půl milionu korun. Projekt společnosti LOréal a Světové organizace UNESCO podporuje mladé talentované badatelky po celém světě již 19 let, v České republice jde o dvanáctý ročník. Zúčastněné mají možnost získat výhru v hodnotě 250 000 Kč, a to ve dvou věkových kategoriích. Ocenění jim umožní jak profesní, tak osobní růst. Přihlašovat své projekty mohou od 1. prosince až do 31. ledna 2018 prostřednictvím internetové stránky www.prozenyvevede.cz. ...
duna [germánske jazyky], presyp - akumulačná forma georeliéfu vysoká spravidla do 50 m. Utvára sa ukladaním vetrom prenášaného jemného piesku (eolických pieskov) v okolí prekážok, ktoré znižujú rýchlosť vetra.. V závislosti od tvaru a polohy vzhľadom na prevládajúci smer vetra sa rozlišuje viacero typov dún: priečne duny utvárajú chrbty pretiahnuté kolmo na smer vetra, pozdĺžne duny sa tiahnu v smere vetra, barchany majú polmesiacovitý pôdorys s výbežkami v smere prevládajúceho vetra, parabolické duny majú rovnaký pôdorys ako barchany, ale výbežky orientované proti smeru vetra, pyramidálne duny formované premenlivými vetrami na pobrežiach sú najmohutnejšie, často vysoké viac ako 150 m. Spájaním rôznych typov dún vznikajú komplexné presypy (presypové polia).. Duny sú typické pre púšťové oblasti, vyskytujú sa však často aj na piesočnatých morských pobrežiach. Na nížinách Slovenska, najmä v Borskej nížine, vznikali v ...
duna [germánske jazyky], presyp - akumulačná forma georeliéfu vysoká spravidla do 50 m. Utvára sa ukladaním vetrom prenášaného jemného piesku (eolických pieskov) v okolí prekážok, ktoré znižujú rýchlosť vetra.. V závislosti od tvaru a polohy vzhľadom na prevládajúci smer vetra sa rozlišuje viacero typov dún: priečne duny utvárajú chrbty pretiahnuté kolmo na smer vetra, pozdĺžne duny sa tiahnu v smere vetra, barchany majú polmesiacovitý pôdorys s výbežkami v smere prevládajúceho vetra, parabolické duny majú rovnaký pôdorys ako barchany, ale výbežky orientované proti smeru vetra, pyramidálne duny formované premenlivými vetrami na pobrežiach sú najmohutnejšie, často vysoké viac ako 150 m. Spájaním rôznych typov dún vznikajú komplexné presypy (presypové polia).. Duny sú typické pre púšťové oblasti, vyskytujú sa však často aj na piesočnatých morských pobrežiach. Na nížinách Slovenska, najmä v Borskej nížine, vznikali v ...
ve u krach cestoviek nehroz , tak e zost va len aby sa aj nejak v ber poistn ho zabezpe il. Naozaj nech pem, o om t novela z kona bola, asi zrejme len tak populistick krok na kor z kazn kov. Tak e len tak alej, d fam, e si v bud cnosti ka d dobre rozmysl , i d vopred nejak z lohu alebo rad ej po k na ten last minute. udia tie peniaze u neuvidia, to je viac ako ist . ...
Gramovo farbenie zaviedol v roku 1884 Christian Gram. Je to diferenciačné farbenie založené na sfarbení gram-pozitívnych a gram-negatívnych buniek baktérií. Rozdiel medzi týmito dvoma bunkami je predovšetkým v ich bunkovej stene. Bunkové steny G+ baktérií majú oveľa hrubšiu vrstvu peptidoglykánu ako bunkové steny G- baktérií. G- bunky majú vo vonkajšej bunkovej stene aj množstvo lipidov. Princíp Gramovo farbenia spočíva v tom, že sa obidve bunky (G+ aj G-) zafarbia farbivom kryštálovou violeťou, čím sa obe sfarbia do fialova. Preparát sa potom morí jódom v roztoku jodidu draselného, ktorý s farbivom vytvorí komplex v obidvoch bunkách. Potom sa farbivo vymýva etanolom (alebo acetónom), pričom komplex sa vyplavuje len z G- baktérií (rozpúšťa sa vonkajšia lipidová vrstva bunkovej steny), ktoré sa odfarbia. Napokon sa preparát dofarbuje karbolfuchsínom (alebo safranínom). G+ bunky teda po Gramovom farbení ostávajú fialové, G- bunky sú ...
... heme/globin-containing molecules (even monomeric globin ones) that deal with gas-binding are referred to as oxyhemoglobins. In ... Nitric oxide can also be transported by hemoglobin; it is bound to specific thiol groups in the globin protein to form an S- ... NO binds reversibly to a specific cysteine residue in globin; the binding depends on the state (R or T) of the hemoglobin. The ... Such a name is given because this arrangement is the same folding motif used in other heme/globin proteins such as myoglobin. ...
"Regulation of Globin Gene Expression". Cite journal requires ,journal= (help) "World Renowned Geneticist Richard Myers to Speak ... His team sought to understand globin gene expression, studying both cis- and trans-acting components that regulate ...
Marotta CA, Wilson JT, Forget BG, Weissman SM (July 1977). "Human beta-globin messenger RNA. III. Nucleotide sequences derived ... it was known that the disease was caused by a mutation in the β-globin gene. In 1977, in the third of a series of 3 research ...
The β-globin LCR in mice and humans is found 6-22 kb upstream of the first globin gene (epsilon). It controls the following ... The β-globin LCR was identified over 20 years ago in studies of transgenic mice. These studies determined that the LCR was ... Although the name implies that the LCR is limited to a single region, this implication only applies to the β-globin LCR (HBB- ... It functions in a copy number-dependent manner and is tissue-specific, as seen in the selective expression of β-globin genes in ...
Efstratiadis, A.; Kafatos, F. C.; Maxam, A. M.; Maniatis, T. (1976). "Enzymatic in vitro synthesis of globin genes". Cell. 7 (2 ...
Proudfoot NJ, Maniatis T (1980). "The structure of a human alpha-globin pseudogene and its relationship to alpha-globin gene ... Proudfoot NJ, Gil A, Maniatis T (1983). "The structure of the human zeta-globin gene and a closely linked, nearly identical ... Goodbourn SE, Higgs DR, Clegg JB, Weatherall DJ (1983). "Molecular basis of length polymorphism in the human zeta-globin gene ... 1974). "Nucleotide sequences of human globin messenger RNA". Proc. Natl. Acad. Sci. U.S.A. 71 (6): 2300-4. Bibcode:1974PNAS... ...
ISBN 978-0-8018-5884-0. James E. Bowman (1983). Distribution and Evolution of Hemoglobin and Globin Loci. Proceedings of the ... Fourth Annual Comprehensive Sickle Cell Center Symposium on the Distribution and Evolution of Hemoglobin and Globin Loci at the ...
Theta-globin mRNA is found in human fetal erythroid tissue but not in adult erythroid or other nonerythroid tissue. The theta-1 ... Theta-1 is a member of the human alpha-globin gene cluster that involves five functional genes and two pseudogenes. The order ... Gonzalez-Redondo JM, Han IS, Gu YC, Huisman TH (1988). "Nucleotide sequence of the human theta 1-globin gene". Biochem. Genet. ... Ley TJ, Maloney KA, Gordon JI, Schwartz AL (1989). "Globin gene expression in erythroid human fetal liver cells". J. Clin. ...
... zeta globins) and two ε globins (epsilon globins) (ζ2ε2) Hb Gower-2, composed of two alpha globins and two epsilon globins ( ... α2ε2) Hb Portland, composed of two zeta globins and two gamma globins (ζ2γ2) Fetal Hb (Hb F) is produced from approximately ... Each globin chain is associated with an iron-containing heme moiety. Throughout life, the synthesis of the alpha-like and the ... Globin chains: Many of the clinically important hemoglobinopathies are caused by missense mutations in the coding sequence of a ...
"Adaptive Functional Divergence Among Triplicated α-Globin Genes in Rodents". Genetics. 178 (3): 1623-1638. doi:10.1534/genetics ...
In the vast majority of vertebrates there are distinct embryonic, foetal and adult globins. His early work was directed at ... Gardening and Reading Maclean's career began with research attempts to understand the developmental switching of globin genes. ... trying to reactivate foetal globin expression, chiefly working with the amphibian Xenopus and chickens. He was, however, ...
Globin superfamily - Members share an 8-alpha helix globular globin fold. Immunoglobulin superfamily - Members share a sandwich ...
... and β-Thalassemias in Mice by Expression of Human Embryonic Globins". Blood. 92 (9): 3057-3063. Huehns, E.R.; Flynn, F.V.; ...
Cite journal requires ,journal= (help) Ingram VM (October 1956). "A specific chemical difference between the globins of normal ...
Itano also found that the globin portion of sickle cell hemoglobin had a barely detectable difference in electrical charge. To ... Ingram, V.M. (13 October 1956). "A specific chemical difference between the globins of normal human and sickle-cell anaemia ...
... it can result in either a reduced or absent globin chain production. If beta thalassaemia major is left untreated or under ...
Costantini F, Lacy E (November 1981). "Introduction of a rabbit beta-globin gene into the mouse germ line". Nature. 294 (5836 ...
Differences in the regulated expression of cloned human alpha globin and beta globin genes introduced into MEL cells: the role ... Basis for regulating the expression of human alpha- and beta-globin genes. Discovery of a family of vertebrate genes encoding ... Transcriptional regulation of globin gene expression in the human erythroid cell line K562 », Science, (1983), 220, p. 1281- ... where he studied the molecular basis for the regulation of globin gene expression. In 1984, he joined the European Molecular ...
... many globins form a family though some members have sequence identities of only 15%. Superfamily (probable common evolutionary ...
The term globin can refer more specifically to proteins including the globin fold. The term globular protein is quite old ( ... Globins at the US National Library of Medicine Medical Subject Headings (MeSH) Travaglini-Allocatelli C, Ivarsson Y, Jemth P, ... a member of the globin protein family. Other globular proteins are the alpha, beta and gamma (IgA, IgD, IgE, IgG and IgM) ...
In 1978, the 5' UTR of the human gamma-globin mRNA was fully sequenced. In 1980, a study was conducted on the 3' UTR of the ... Michelson, A. M.; Orkin, S. H. (1980-11-01). "The 3' untranslated regions of the duplicated human alpha-globin genes are ... untranslated region of human gamma-globin mRNA". Nucleic Acids Research. 5 (10): 3515-3522. doi:10.1093/nar/5.10.3515. ISSN ... duplicated human alpha-globin genes. The untranslated region is seen in prokaryotes and eukaryotes, although the length and ...
Beta-thalassemia is a genetic disease mostly caused by beta-globin gene mutations. Clinical diagnosis is based on ...
1995). "Evidence on primate phylogeny from ε-globin gene sequences and flanking regions". Journal of Molecular Evolution. 40 (1 ...
It is the first haemoglobin discovered from bacteria, but unlike classic hemoglobin it is composed only of a single globin ... The amino acid sequence revealed that it is made up of a single globin domain without additional structural elements, in ... Dikshit KL, Webster DA (1988). "Cloning, characterization and expression of the bacterial globin gene from Vitreoscilla in ... solution of its crystal structure confirmed that the three-dimensional structure of is remarkably similar to the classic globin ...
For example, ATRX mutations affect the expression of alpha-globin gene cluster, causing alpha-thalassemia". ATRX interacts with ... the transcription co-factor DAXX and the alpha-globin gene cluster. Together they are all responsible for depositing the ...
Human globin genes were microinjected into mouse fibroblasts and into mouse oocytes and shown to express human globin mRNA. ... The rabbit ribosome cell-free system was able to produce normal human globin from normal human mRNA, sickle cell globin from ... Transfer of human and murine globin-gene sequences into transgenic mice. Am. J. Hum. Genet.• 37: 295-310, 1985. Anderson, W.F ... Replication and expression of thymidine kinase and human globin genes microinjected into mouse fibroblasts. Proc. Natl. Acad. ...
"Expression of miR-210 during erythroid differentiation and induction of gamma-globin gene expression". BMB Reports. 42 (8): 493 ...
has four kinds of globin chains and two kinds of linker chains, Sabella spallanzanii has three globin chains and three linker ... July 2001). "The primary structure of globin and linker chains from the chlorocruorin of the polychaete Sabella spallanzanii". ... Giant hemoglobin is composed of multiple heme-containing globin chains and linker (InterPro: IPR031639) chains. Each species ...
The βE mutation affects β-gene expression creating an alternate splicing site in the mRNA at codons 25-27 of the β-globin gene ... Also, this hemoglobin variant has a weak union between α- and β-globin, causing instability when there is a high amount of ... 1984). "Hemoglobin E in Europeans: Further Evidence for Multiple Origins of the βE-Globin Gene". Am J Hum Genet. 36 (1): 212- ...
A few years later, Oliver Smithies and she followed up on her earlier research on globins, and they discovered the different ... Her work characterized variants of globins, the family of proteins responsible for transporting blood in oxygen, and in 1984, ... After completing her doctorate, Bowman began studying variants of globins with Vernon Ingram at the Massachusetts Institute of ...
biochemistry) Any globular protein that incorporates a globin fold. *(biochemistry) One of several polypeptides that are the ... Retrieved from "https://en.wiktionary.org/w/index.php?title=globin&oldid=48058080" ...
... beta-globin type is a condition that affects the function of red blood cells. Explore symptoms, inheritance, genetics of this ... HBB gene mutations that cause methemoglobinemia, beta-globin type change the structure of beta-globin and promote the heme iron ... This gene provides instructions for making a protein called beta-globin. Beta-globin is one of four components (subunits) that ... In adults, hemoglobin normally contains two subunits of beta-globin and two subunits of another protein called alpha-globin. ...
Globin_like (cd01067). Accession cd01067 Integration. RsbS co-antagonist protein RsbRA N-terminal domain (IPR014792) Member ...
Globin - The protein component of hemoglobi, is clearly explained in Medindia s glossary of medical terms ... Globin - Glossary. Written & Compiled by Medindia Content Team. Medically Reviewed by The Medindia Medical Review Team on May ...
Alteration of balanced expression of globin genes, which usually occurs due to damage to adult β-globin genes, leads to ... The phenomenon of stage-specific transcription of globin genes is referred to as globin gene switching. Mechanisms of ... HS4 core element of the human beta-globin locus control region is required for high-level globin gene expression in definitive ... The hematopoietic regulator TAL1 is required for chromatin looping between the beta-globin LCR and human gamma-globin genes to ...
MSKs innovative globin gene transfer therapy offers the potential to free patients from a lifetime of red blood cell ... which is believed to achieve better expression of β-globin on a per-copy basis, and therefore the potential for superior ... utilizing a lentiviral vector to stably insert a functional β-globin gene, and then infusing the patient with engineered HSCs ...
Belongs to the globin family.PROSITE-ProRule annotation. ,p>Manual validated information which has been generated by the ... sp,Q7SID0,GLBF1_EPTBU Globin-F1 OS=Eptatretus burgeri PE=1 SV=1 PIIDQGPLPTLTDGDKKAINKIWPKIYKEYEQYSLNILLRFLKCFPQAQASFPKFSTKKS ...
Belongs to the globin family.PROSITE-ProRule annotation. ,p>Manual validated information which has been generated by the ... sp,P02207,GLB_LAMFL Globin OS=Lampetra fluviatilis OX=7748 PE=1 SV=2 ...
Fine tuning of globin gene expression by DNA methylation.. Goren A1, Simchen G, Fibach E, Szabo PE, Tanimoto K, Chakalova L, ... γ/γ+β was calculated on the basis of total γ globin (γA+γG).. Results (average of 3 experiments) for real time PCR are included ... Levels of globin expression were obtained from dilution analysis and compared to Aprt (set to 1) in the same cells. Each ... Results for β globin are presented for comparison.. The data shown for non-erythroid cells was obtained using mononucleosomes ...
... upstream of the epsilon-globin gene. Addition of these sites confers copy number dependent expression on the human beta-globin ... The beta-globin dominant control region: hypersensitive site 2.. Philipsen S1, Talbot D, Fraser P, Grosveld F. ... The Dominant Control Region (DCR) of the human beta-globin gene locus consists of four strong hypersensitive sites (HSS) ... The significance of these results for the regulation of globin gene expression is discussed. ...
β-Globin Intergenic Transcription and Histone Acetylation Dependent on an Enhancer AeRi Kim, Hui Zhao, Ina Ifrim, Ann Dean ... Subcellular Transport of EKLF and Switch-On of Murine Adult βmaj Globin Gene Transcription Yu-Chiau Shyu, Tung-Liang Lee, Shau- ... GATA-1 Modulates the Chromatin Structure and Activity of the Chicken α-Globin 3′ Enhancer Martín Escamilla-Del-Arenal, Félix ... CpG Hypomethylation in a Large Domain Encompassing the Embryonic β-Like Globin Genes in Primitive Erythrocytes Mei Hsu, Rodwell ...
The mammalian beta-globin locus is a multigene locus containing several globin genes and a number of regulatory elements. ... The mammalian beta-globin locus is a multigene locus containing several globin genes and a number of regulatory elements. ... Joining the loops: beta-globin gene regulation IUBMB Life. 2008 Dec;60(12):824-33. doi: 10.1002/iub.129. ... The discovery of the LCR initially raised the question how this element could exert its effect on the downstream globin genes. ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Roy J, Sen Santara S, Adhikari A, Mukherjee A, Adak S. Control of catalysis in globin coupled adenylate cyclase by a globin-B ... Delayed globin synthesis leads to excess heme and the macrocytic anemia of Diamond Blackfan anemia and del(5q) myelodysplastic ... "Globins" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject Headings) ... A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME ...
Our dedicated kits are specifically designed for highly efficient rRNA removal and globin mRNA removal for a range of ... Ribosomal RNA and globin mRNA removal. Efficient ribosomal RNA and globin mRNA removal. To maximize your unique sequencing ... For rapid rRNA and/or globin mRNA removal for RNA-seq library preparation from human, mouse, rat and other mammalian samples ... Our dedicated kits are specifically designed for highly efficient rRNA removal and globin mRNA removal to suit your specific ...
Heme activates globin transcription and translation; therefore, heme synthesis must precede globin synthesis. As free heme is a ... before ample globin is produced. From the CFU-E/proerythroblast (CD71+ Ter119- cells) stage onward, erythroid progenitors ...
Incidence of methemoglobinemia in patients with hematologic malignancy or aplastic anemia who received dapsone prophylaxis through a retrospective chart review encompassing the last 15 ...
Hemoglobin-like proteins in bacteria Bacterial globins are proteins possessing the classical globin fold and the highly ... myoglobin-like globins (two- or single-domain proteins), sensor globins, and truncated globins. NO detoxification is a well- ... Globins are an ancient superfamily of diverse proteins (Vinogradov et al. 2006). The first report of a microbial globin was in ... Bacterial globins are proteins possessing the classical globin fold and the highly conserved active site residues required for ...
Globins. Lecture 10/01/2009. The Backbone structure of Myoglobin. 2. Myoglobin: 44 x 44 x 25 Å single subunit 153 amino acid ... Globins & Enzyme Catalysis -Globins & enzyme catalysis. 10/06/2009. the bohr effect. higher ph i.e. lower [h + ] promotes ... EVOLUTION OF GLOBINS -. evolution of globins evolution of visual pigments and related molecules. evolution of gene clusters. ... Globins & Enzyme Catalysis -. 10/06/2009. the bohr effect. higher ph i.e. lower [h + ] promotes tighter binding of oxygen to ...
... in which the globin has been obtained from whole blood by depigmentation in a medium tha ... globin that is insoluble at neutral pH, and therefore at physiological pH, ... Preparation of a Directly Sterile Globin Powder or Paste or Globin Based Material. The liquid or solid globin materials of ... a material that comprises globin that is insoluble at physiological pH and that also comprises globin that is soluble at ...
In addition, our findings provide a mechanism for understanding the high levels of γ-globin transcription seen in patients with ... demonstrate that DNA methylation serves as an elegant in vivo fine-tuning device for selecting appropriate genes in the globin ... Expression patterns in the globin gene cluster are subject to developmental regulation in vivo. While the γA and γG genes are ... Hereditary Persistence of Fetal Hemoglobin, and help explain why 5azaC and butyrate compounds stimulate γ-globin expression in ...
They include epsilon-globin, gamma-globin, delta-globin and beta-globin. There is also a pseudogene of beta (theta-beta) in the ... Adult HEMOGLOBIN is comprised of two ALPHA-GLOBIN chains and two beta-globin chains. ... Members of the beta-globin family. In humans, they are encoded in a gene cluster on CHROMOSOME 11. ... beta Globin; Non-alpha Globin Chain, Unspecified; Non alpha Globin Chain, Unspecified; beta Globins; beta-Globin ...
Depletes alpha and beta globin mRNA from blood total RNA with a simple magnetic bead procedure (no enzymatic treatments) ... GLOBINclear-Human Globin mRNA Removal Kit Depletes alpha and beta globin mRNA from blood total RNA with a simple magnetic bead ... Globin Transcript Removal Ambions GLOBINclear-Human Kit is designed to rapidly deplete alpha and beta globin mRNA from total ... GLOBINclear-Human Globin mRNA Removal Kit Depletes alpha and beta globin mRNA from blood total RNA with a simple magnetic bead ...
Restriction fragment length polymorphism analysis of the beta-globin cluster of these … ... Association of thalassaemia intermedia with a beta-globin gene haplotype Br J Haematol. 1987 Mar;65(3):367-73. doi: 10.1111/j. ... This beta haplotype is linked to a DNA sequence variation 5 (at position -158) to the G gamma globin gene which can be ... beta-globin haplotype (-+-++), in contrast to 1/42 of the thalassaemia major patients. Furthermore, the -+-++ beta haplotype is ...
Ann Dean on The beta-globin locus, part of a collection of online lectures. ... Two so-called beta-like globin chains and two alpha-like globin chains. In each tetramer, the four globin chains are held ... and beta globin chains leads to anemia. How the alpha and beta globin genes achieve this balanced protein production is not ... The beta globin locus has long served as a major paradigm for studies of eukaryotic gene regulation and transcription. In ...
Developmental specificity of recruitment of TBP to the TATA box of the human γ-globin gene. Zhi-Jun Duan, Xiangdong Fang, Alex ... The in vitro γ-globin gene expression depends upon an intact TATA box and recruitment of TBP. (A) The γTATA binds TBP, and the ... The initiation site of the mRNA transcribed from the TATA box-mutated γ-globin gene is shown in lane 2 (d10 yolk sac) and lane ... Recruitment of TBP, TFIIB, and Pol II in the transgenic mice carrying the TATA box-mutated γ-globin gene. The day-11 yolk sac ...
Crystal structure of cytoglobin: the fourth globin type discovered in man displays heme hexa-coordination.. de Sanctis, D., ... The crystal structure of cytoglobin: the fourth globin type discovered in man. *DOI: 10.2210/pdb1UMO/pdb ... Cytoglobin is a recently discovered hemeprotein belonging to the globin superfamily together with hemoglobin, myoglobin and ... Cytoglobin is a recently discovered hemeprotein belonging to the globin superfamily together with hemoglobin, myoglobin and ...
... Takaras Human Beta-globin Control Primer Set contains a set of PCR primers that ... The Human Beta-globin Control Primer Set may be used as a experimental control during protocols such as PCR. Primer Sequences. ... Beta-globin makes up about half of the human hemoglobin tertrameric protein; in the normal human adult, the hemoglobin tetramer ... Products , PCR , Pathogen_Detection_and_Screening_Kits , Human_Pathogen_Detection , Human_Beta-globin_Control_Primer_Set. ...
The alpha-globin genes are on chromosome 16, and the beta-globin genes are on chromosome 11. And even among the beta-globin ... Two are alpha-globins and two are beta-globins." (The proteins are named globins, I learned later, reading Goldstrohms thesis ... "If you look at contemporary humans," Hardison added, "we have several alpha-globin genes and several beta-globin genes. ... And, Hardison noted, "everyone who has a bad beta-globin gene also has a good fetal globin gene. ...
Five polymorphic sites in the β-globin gene cluster were analyzed ... To analyze the frequency of the haplotypes of β-globin gene cluster in randomly selected patients with sickle cell disease (SCD ... 0/Hemoglobin, Sickle; 0/beta-Globins; 9034-63-3/Fetal Hemoglobin From MEDLINE®/PubMed®, a database of the U.S. National Library ... OBJECTIVE: To analyze the frequency of the haplotypes of β-globin gene cluster in randomly selected patients with sickle cell ...
  • The phenomenon of stage-specific transcription of globin genes is referred to as globin gene switching. (springer.com)
  • Mechanisms of expression switching, stage-specific activation, and repression of transcription of α- and β-globin genes are of interest from both theoretical and practical points of view. (springer.com)
  • Alteration of balanced expression of globin genes, which usually occurs due to damage to adult β-globin genes, leads to development of severe diseases-hemoglobinopathies. (springer.com)
  • In most cases, reactivation of the fetal hemoglobin gene in patients with β-thalassemia and sickle cell disease can reduce negative consequences of irreversible alterations of expression of the β-globin genes. (springer.com)
  • This review focuses on the current state of research on genetic and epigenetic mechanisms underlying stage-specific switching of β-globin genes. (springer.com)
  • These studies demonstrate that DNA methylation serves as an elegant in vivo fine-tuning device for selecting appropriate genes in the globin locus. (nih.gov)
  • Addition of these sites confers copy number dependent expression on the human beta-globin gene in murine erythroleukaemia cells and transgenic mice, at levels comparable with the endogenous mouse globin genes. (nih.gov)
  • The mammalian beta-globin locus is a multigene locus containing several globin genes and a number of regulatory elements. (nih.gov)
  • The most important regulatory element in the locus is the locus control region (LCR) upstream of the globin genes that is essential for high-level expression of these genes. (nih.gov)
  • The discovery of the LCR initially raised the question how this element could exert its effect on the downstream globin genes. (nih.gov)
  • The question was solved by the finding that the LCR and activate globin genes are in physical contact, forming a chromatin structure named the active chromatin hub (ACH). (nih.gov)
  • In adults, during the later stages of erythroid differentiation, the genes in both the alpha and beta globin loci are expressed at exceptionally high rates. (hstalks.com)
  • How the alpha and beta globin genes achieve this balanced protein production is not known. (hstalks.com)
  • If you look at contemporary humans," Hardison added, "we have several alpha-globin genes and several beta-globin genes. (psu.edu)
  • The alpha-globin genes are on chromosome 16, and the beta-globin genes are on chromosome 11. (psu.edu)
  • METHODS: Five polymorphic sites in the β-globin gene cluster were analyzed by polymerase chain reaction (PCR) followed by restriction digestion and agarose gel electrophoresis in a total of 100 patients, including 95 homozygous for HbS (sickle cell anemia) and 5 compound heterozygotes for HbS and HbC genes (HbSC disease). (biomedsearch.com)
  • Here we report a survey of nucleotide variation in the adult globin genes of house mice from South America. (genetics.org)
  • HEB, E2A and ETO-2 significantly interact with locus control region (LCR) and promoters of globin genes, and their relative ratio is altered during erythropoiesis. (umontreal.ca)
  • Strikingly and consistent with the expression of globin genes, we characterized transcription factors involved in open chromatin configuration and basal level of globin gene expression in lymphoid progenitor cells. (umontreal.ca)
  • Recent research confirms that the HBBP1 region of the 6-gene β-globulin cluster is highly non-variable compared to the other β-globin genes based on large-scale DNA diversity assessment within both humans and chimpanzees. (blogspot.com)
  • The most significant genetic factor in cis associated with high HbF is Xmn I polymorphism located at −158 upstream to the G γ globin genes [ 9 ]. (hindawi.com)
  • We have analyzed the nuclear positioning of the coordinately regulated α- and β-globin genes and show that the gene-dense chromatin surrounding the human α-globin genes is frequently decondensed, independent of transcription. (rupress.org)
  • Against this background, we show the frequent juxtaposition of active α- and β-globin genes and of homologous α-globin loci that occurs at nuclear speckles and correlates with transcription. (rupress.org)
  • The same degree of proximity does not occur between human β-globin genes or between murine globin genes, which are more constrained to their chromosome territories. (rupress.org)
  • Our findings suggest that the distribution of globin genes within erythroblast nuclei is the result of a self-organizing process, involving transcriptional status, diffusional ability of chromatin, and physical interactions with nuclear proteins, rather than a directed form of higher-order control. (rupress.org)
  • To address whether nuclear organization has a functional role, we have chosen to follow the behavior of the coregulated α- and β-globin genes in primary human erythroblasts during terminal erythroid differentiation ( Wickramasinghe, 1975 ). (rupress.org)
  • This balance is achieved despite the fact that the α- and β-globin genes lie on separate chromosomes and in very different chromatin contexts. (rupress.org)
  • The human β-globin gene cluster is located on chromosome 11 and encodes the five β-like globin genes: ɛ-, G γ-, A γ- δ-, and β-globin. (haematologica.org)
  • The vertebrate globin genes encoding the α- and β-subunits of the tetrameric hemoglobins are clustered at two unlinked loci. (bibsys.no)
  • The highly conserved linear order of the genes flanking the hemoglobins provides a strong anchor for inferring common ancestry of the globin clusters. (bibsys.no)
  • In fish, the number of α-β-linked globin genes varies considerably between different sublineages and seems to be related to prevailing physico-chemical conditions. (bibsys.no)
  • The Atlantic cod genome was shown to contain 14 globin genes, including nine hemoglobin genes organized in two unlinked clusters designated β5-α1-β1-α4 and β3-β4-α2-α3-β2. (bibsys.no)
  • In silico analysis of the six teleost genomes available showed that the two α-β globin clusters are flanked by paralogs of five duplicated genes, in agreement with the proposed teleost-specific duplication of the ancestral vertebrate globin cluster. (bibsys.no)
  • Screening the genome of extant urochordate and cephalochordate species for conserved globin-flanking genes revealed linkage of RHBDF1, MPG and ARHGAP17 to globin genes in the tunicate Ciona intestinalis, while these genes together with LCMT are closely positioned in amphioxus (Branchiostoma floridae), but seem to be unlinked to the multiple globin genes identified in this species. (bibsys.no)
  • The proximity of globin-flanking genes in the tunicate and amphioxus genomes resembles the RHBDF1-MPG-α-globin-ARHGAP17-LCMT linked genes in man and chicken. (bibsys.no)
  • To date only three duplication/inserts of more than 20 nucleotides have been described for the globin genes. (haematologica.org)
  • Restriction endonuclease mapping of cellular DNA has been used to identify chromosomes that carry the mutant Hb Presbyterian β-globin genes in a family with individuals heterozygous for this disease. (springer.com)
  • Jeffreys AJ (1979) DNA sequence variants in the G γ-, A γ-, δ and β-globin genes of man. (springer.com)
  • Phillips JA, Pawny SR, Kazazian HH Jr, Boehm CO, Scott AF, Smith KO (1980) Prenatal diagnosis of sickle cell anemia by restriction endonuclease analysis: Hind III polymorphisms in γ-globin genes extend test applicability. (springer.com)
  • Wilson JT, Wilson JB, DeRiel JK, Villa-Komaroff L, Efstratiadis A, Forget BG, Weissman SM (1978) Insertion of synthetic copies of human globin genes into bacterial plasmids. (springer.com)
  • This assay can be used instead of Southern Blot analysis to determine the total number of intact alpha globin genes. (specialtylabs.com)
  • Amongst the limitations they are faced with is the fact that human embryonic stem cells, due to their origin, produce reticulocytes expressing foetal rather than adult haemoglobin, caused by developmentally regulated genes at the β-globin locus. (gla.ac.uk)
  • This cluster consists of five β-like globin genes arranged sequentially in the order they are expressed during development. (gla.ac.uk)
  • Reticulocytes derived from cord blood haematopoietic stem cells or embryonic pluripotent stem cells primarily express the foetal γ- and embryonic ε-globin genes. (gla.ac.uk)
  • Here, we used the CRISPR/Cas9 system to create different deletions or mutations at the β-globin locus in K562 cells, a human erythroid cancer cell line which expresses embryonic and foetal globin genes. (gla.ac.uk)
  • Co-inheritance of the rare β hemoglobin variants Hb Yaounde, Hb Görwihl and Hb City of Hope with other alterations in globin genes: impact in genetic counseling. (semanticscholar.org)
  • Sjakste, T. 2004-10-13 00:00:00 The data on the structure of gene domains of both mammalian and avian α- and β-globin genes are reviewed. (deepdyve.com)
  • The avian β-globin genes are specifically arranged and their expression is less dependent from the locus control region. (deepdyve.com)
  • An unidentified housekeeping gene as well as some other transcripts not encoding the structural globin genes is transcribed in the direction opposite to that of the globin genes in both mammalian and avian domains. (deepdyve.com)
  • In comparison with the homologous gene clusters in mammals, the low retention rate for lineage-specific gene duplicates in the avian globin gene clusters suggests that the developmental regulation of Hb synthesis in birds may be more highly conserved, with orthologous genes having similar stage-specific expression profiles and similar functional properties in disparate taxa. (unl.edu)
  • Haemoglobins were analysed by ion-exchange HPLC (Variant II) and capillary electrophoresis (Sebia Capillarys Flex) and DNA by automatic Sanger sequencing of δ-globin and β-globin genes. (bmj.com)
  • Concerted evolution of α globin genes in Podolian cattle (Bos taurus primigenius) and river buffalo (Bubalus bubalis)? (biochemsoctrans.org)
  • We address this issue by using as a highly informative system the duplicated alpha-globin genes in which ectopic recombination can lead to gene deletions, often very prevalent in populations affected by malaria, as well as reduplications. (le.ac.uk)
  • Our study demonstrates that CSDA acts as a repressor of gamma-globin genes in vivo and is a novel quantitative trait locus for HPFH. (unina.it)
  • G/Aγ, intergenic region between Gγ- and Aγ-globin genes. (nih.gov)
  • The beta-like hemoglobins include the epsilon, gamma, beta, and delta globins, whose genes are present on chromosome 11 in a linked cluster (ie, the beta globin complex). (testcatalog.org)
  • The genes produce gamma globin chains that form tetramers with alpha globin chains to create fetal hemoglobin (Hb F). HBG1 and HBG2 differ only in which amino acid is located at position 136 (alanine or glycine). (testcatalog.org)
  • Additionally, some alterations in the promoter regions of the gamma globin genes are known to cause a form of hereditary persistence of fetal hemoglobin (HPFH), which is characterized by a significant but harmless elevation of Hb F into adulthood. (testcatalog.org)
  • We describe a family in which alpha-thalassemia occurs in association with a deletion of 62 kilobases from a region upstream of the alpha globin genes. (ox.ac.uk)
  • Hence hemoglobins and the globin genes encoding them have been an important system for investigating many biochemical and evolutionary issues. (semanticscholar.org)
  • Alpha thalassaemia and extended alpha globin genes in Sri Lanka. (ox.ac.uk)
  • The α-globin genes were studied in nine families with unexplained hypochromic anaemia and in 167 patients with HbE β thalassaemia in Sri Lanka. (ox.ac.uk)
  • The human γ-globin genes (both Aγ and Gγ-globin genes) carry three Oct-1 transcription factor consensus sequences within their promoter regions. (wayne.edu)
  • These results suggest that the decoy oligonucleotide designed for the Oct-1 transcription factor consensus sequence could induce expression of the endogenous γ-globin gene through competitive binding of the Oct-1 transcription factor, resulting in activation of the γ-globin genes. (wayne.edu)
  • Therefore, disrupting the bindings of the Oct-1 transcriptional factors with the decoy oligonucleotide provides a novel approach for inducing expression of the γ-globin genes. (wayne.edu)
  • In silico analysis of the genome of Caenorhabditis elegans revealed an unexpectedly high number of globin genes featuring a remarkable diversity in gene structure, amino acid sequence and expression profiles. (wayne.edu)
  • We also show that the Caenorhabditis globin genes are expressed in distinct, mostly non-overlapping, sets of cells and that they are all under strong purifying selection. (wayne.edu)
  • A duplication of an ancestral globin gene occurred before the divergence of the Platyhelminthes and the Nematoda and one of the duplicated genes radiated further in the nematode phylum before the split of the Spirurina and Rhabditina and was followed by further radiation in the lineage leading to Caenorhabditis. (wayne.edu)
  • The resulting globin genes were subject to processes of subfunctionalization and diversification leading to cell-specific expression patterns. (wayne.edu)
  • The existence of small "silent" deletions in the beta-globin gene cluster emphasizes the importance of deletion size in altering expression of the fetal globin genes. (ox.ac.uk)
  • Although several genomes of amoebozoan species have been sequenced, little is known about the phyletic distribution of globin genes within this phylum. (ijbs.com)
  • Only two flavohemoglobins (FHbs) of D. discoideum have been reported and characterized previously while the genomes of Entamoeba species are apparently devoid of globin genes. (ijbs.com)
  • We investigated eleven amoebozoan species for the presence of globin genes by genomic and phylogenetic in silico analyses. (ijbs.com)
  • Phylogenetic evidence suggests that these globin genes were independently acquired via horizontal gene transfer from some ancestral bacteria. (ijbs.com)
  • There are two main classes of thalassemia, α and β, in which the α- and β-globin genes are involved, and rarer forms caused by abnormalities of other globin genes. (mhmedical.com)
  • Our dedicated kits are specifically designed for highly efficient rRNA removal and globin mRNA removal to suit your specific applications. (qiagen.com)
  • One obstacle for expression profiling RNA from whole blood is the relatively high content of globin messenger RNA (mRNA) from immature red blood cells. (bio-medicine.org)
  • In fact, up to 70% of the mRNA mass is from globin transcripts. (bio-medicine.org)
  • Ambion's GLOBINclear-Human Kit is designed to rapidly deplete alpha and beta globin mRNA from total RNA preparations derived from human whole blood. (bio-medicine.org)
  • The kit employs a novel hybridization capture technology (see "Simple, Effective Globin mRNA Reduction Protocol" at right) that uses the power of biotin/streptavidin binding and the specificity of nucleic acid hybridization to effectively remove 9099.5% globin transcripts from blood total RNA (Figure 1). (bio-medicine.org)
  • To further test the specificity of globin mRNA reduction, synthetic globin transcripts were added to HeLa cell RNA, and samples were processed or left unprocessed with the GLOBINclear Kit (Figure 2). (bio-medicine.org)
  • Percent Present Calls for Samples Treated or Untreated with GLOBINclear-Human Globin mRNA Removal Kit. (bio-medicine.org)
  • Globin mRNA levels can vary among donors, which can unpredictably affect RNA amplification and array results and therefore, confound interpretations that are made when comparing different samples. (bio-medicine.org)
  • With the removal of globin transcripts, the enriched RNA samples become superior templates for RNA expression profiling because the presence of globin mRNA is no longer a factor in decreasing the sensitivity of gene detection on microarrays (Figure 2). (bio-medicine.org)
  • This kit was developed to reduce or eliminate the negative effects of globin mRNA on high density oligonucleotide expression profiling, and the resulting enriched RNA is compatible with the RiboPure-Blood Kit and the MessageAmp II aRNA Amplification System . (bio-medicine.org)
  • The GLOBINclear Kit contains enough reagents to deplete globin mRNA from 20 samples of total RNA derived from human whole blo od (110 g per sample). (bio-medicine.org)
  • The initiation site of the mRNA transcribed from the TATA box-mutated γ-globin gene is shown in lane 2 (d10 yolk sac) and lane 3 (adult blood). (pnas.org)
  • Beside producing abnormal variant, hemoglobin E (HbE), the G→A substitution in codon 26 (Glu→Lys) of the β -globin gene ( β E ) could also produce β + thalassemia due to decreased functional HbE-mRNA, secondary to alternative splicing mechanism [ 1 ]. (hindawi.com)
  • Contaminating DNA can cause inaccurate RNA quantification and impede proper globin mRNA and rRNA removal. (neb.com)
  • The Ambion® GLOBINclear™-Mouse/Rat Kit employs a novel, non-enzymatic technology that rapidly depletes >95% of the alpha and beta globin mRNA from total RNA preparations derived from whole blood. (thermofisher.com)
  • This band represents globin mRNA, which is expressed at high levels in red blood cells (RBCs) and reticulocytes (RBC precursors). (thermofisher.com)
  • Up to 70% of the mRNA (by mass) in whole blood total RNA are globin transcripts. (thermofisher.com)
  • There are no harsh RNase H enzymatic treatments that may compromise the expression profile by degrading mRNAs other than globin mRNA. (thermofisher.com)
  • This is the case of hydroxyurea (HU), it increases the total intracellular hemoglobin, γ-globin mRNA and Hb F levels. (scielo.br)
  • The repression of globin synthesis was not due to modifications of globin mRNA because the level of globin mRNA and its ability to be translated in vitro were unaffected. (asm.org)
  • In non-heat-shocked reticulocytes, HSP70 mRNA was a moderately abundant mRNA present at 1 to 2% of the level of globin mRNA. (asm.org)
  • Correct human β-globin mRNA has been restored in erythroid cells from transgenic mice carrying the human gene with β-globin IVS2-654 splice mutation and from thalassemia patients with the IVS2-654/β E genotype. (aspetjournals.org)
  • This was accomplished in a dose- and time-dependent manner by free uptake of morpholino oligonucleotide antisense to the aberrant splice site at position 652 of intron 2 in β-globin pre-mRNA. (aspetjournals.org)
  • Under optimal conditions of oligonucleotide uptake, the maximal levels of correct human β-globin mRNA and hemoglobin A in patients' erythroid cells were 77 and 54%, respectively. (aspetjournals.org)
  • Using a differential mRNA display approach, we identified a cDNA of the cold shock domain protein A (CSDA), a trans-acting factor previously reported to interact in vitro with the gamma-globin gene promoter. (unina.it)
  • Real time quantitative analysis in the three patients and CSDA expression studies in the human erythroleukemic K562 cell line showed an inverse relationship between gamma-globin and CSDA mRNA levels. (unina.it)
  • B) Q-RT-PCR analysis of α-globin, β-globin, γ-globin and LYAR gene expression from CB erythroid progenitor cells overexpressing LYAR (LYAR-OE) or containing vector normalized to β-actin mRNA. (nih.gov)
  • D) Q-RT-PCR analysis of α-globin, γ-globin, β-globin or LYAR gene expression from human AE progenitor cells of LYAR-knockdown (KD) or scrambled control (AE) normalized to β-actin mRNA. (nih.gov)
  • When K562 human erythroleukemia cells were treated with the Oct-1 decoy oligonucleotide, significant increases in the level of the γ-globin mRNA were observed. (wayne.edu)
  • The present work contains the description of a clinical case where a PTC, caused by a single nucleotide deletion in the human -globin mRNA, induces accelerated mRNA degradation. (ul.pt)
  • This resistance to decay is further downstream extended when compared with the equivalent effect observed in the human -globin mRNA, and this divergence is shown to be mainly determined by the sequence upstream to the PTC and the secondary structure of the open reading frame (ORF). (ul.pt)
  • Contrary to -globin, the  globin mRNA allows translation reinitiation at a downstream AUG, after translation of a short ORF. (ul.pt)
  • Here, we have used human β‐globin mRNA as a model system to address the role of splicing and polyadenylation for human NMD. (embopress.org)
  • These studies strongly suggest that the presence of a nonsense mutation (but not a missense mutation) in β-globin mRNA decreases the accumulation of its mRNA. (yale.edu)
  • Decreased β-globin mRNA accumulation can be caused by the presence of a nonsense mutation, independent of its type or location. (yale.edu)
  • Methemoglobinemia, beta-globin type is caused by mutations in the HBB gene. (medlineplus.gov)
  • HBB gene mutations that cause methemoglobinemia, beta-globin type change the structure of beta-globin and promote the heme iron to change from ferrous to ferric. (medlineplus.gov)
  • Naturally-occurring mutations show that coordinated regulation of the two loci is required, since imbalance between the alpha and beta globin chains leads to anemia. (hstalks.com)
  • The molecular defects causing β-thalassemia are point mutations predominantly found within and around the β-globin gene which result in reduced or absent synthesis of β-globin 10 . (nature.com)
  • The clinical and genetic data accumulated over several decades through naturally occurring human mutations have identified, two independent pathways that could counter-act the globin imbalance in order to ameliorate the severity of β-thalassaemia 12 . (nature.com)
  • Orkin SH, Kazazian HH Jr, Antonarakis SE, Goff SG, Boehm CO, Sexton JR, Waber PG, Giardina PJV (1982a) Linkage of β-thalassemia mutations and β-globin gene polymorphism with DNA polymorphisms in the human β-globin gene cluster. (springer.com)
  • Mutations that completely inactivate the β gene resulting in no β-globin production cause β0-thalassemia. (alliedacademies.org)
  • Other mutations allow the production of some β globin but in markedly decreased amounts, and are classified as β+-thalassemias. (alliedacademies.org)
  • Human β-globin disorders are relatively common genetic diseases cause by mutations in the β-globin gene. (wayne.edu)
  • The study aim of the study is to characterize the spectrum of β globin gene mutations in 136 Turkish, Northern Iraqi and Albanian pediatric β thalassemia major patients. (pagepressjournals.org)
  • Several hundred different mutations at the α- and β-globin loci have been defined as the cause of the reduced or absent output of α or β chains. (mhmedical.com)
  • A number of nonsense and missense mutations of the β globin gene were constructed by oligonucleotide-directed site-specific mutagenesis. (yale.edu)
  • Gamma globin mutations can manifest either as a quantitative (gamma-thalassemia or nondeletional HPFH) or a qualitative (gamma variant) abnormality. (testcatalog.org)
  • Instead of normal hemoglobin, people with methemoglobinemia, beta-globin type have an abnormal form called methemoglobin, which is unable to efficiently deliver oxygen to the body's tissues. (medlineplus.gov)
  • In methemoglobinemia, beta-globin type, the abnormal hemoglobin gives the blood a brown color. (medlineplus.gov)
  • Beta-globin is one of four components (subunits) that make up hemoglobin. (medlineplus.gov)
  • In adults, hemoglobin normally contains two subunits of beta-globin and two subunits of another protein called alpha-globin. (medlineplus.gov)
  • This potentially curative treatment involves extracting a patient's hematopoietic stem cells (HSCs), utilizing a lentiviral vector to stably insert a functional β-globin gene, and then infusing the patient with engineered HSCs that should now be capable of producing red blood cells and hemoglobin. (mskcc.org)
  • In addition, our findings provide a mechanism for understanding the high levels of gamma-globin transcription seen in patients with Hereditary Persistence of Fetal Hemoglobin, and help explain why 5azaC and butyrate compounds stimulate gamma-globin expression in patients with beta-hemoglobinopathies. (nih.gov)
  • Adult HEMOGLOBIN is comprised of two ALPHA-GLOBIN chains and two beta-globin chains. (curehunter.com)
  • In mammals, the alpha and beta globin loci encode the polypeptides that form the heteromeric hemoglobin protein molecule. (hstalks.com)
  • Cytoglobin is a recently discovered hemeprotein belonging to the globin superfamily together with hemoglobin, myoglobin and neuroglobin. (rcsb.org)
  • It's called hemoglobin," Hardison continued, "because a molecule called a heme, which has iron in it, snuggles right in between the helices of globin proteins. (psu.edu)
  • Hemoglobin comes in at about 500 million years ago, and 50 million years later, its globin component split into alpha and beta subunits. (psu.edu)
  • The alternative two-locus β-globin haplotypes are associated with pronounced differences in intraerythrocyte glutathione and nitric oxide metabolism, suggesting a possible mechanism for selection on hemoglobin function. (genetics.org)
  • Electrophoretic surveys of hemoglobin polymorphism among inbred strains of house mice have revealed two main β-globin variants, HBB-S and HBB-D. Strains that carry the Hbb s haplotype ( e.g . (genetics.org)
  • Sickle cell anemia (SCA) is a monogenic disorder characterized by homozygous inheritance of an abnormal hemoglobin molecule, hemoglobin S (Hb S), due to the substitution of glutamic acid for valine at position 6 of the beta globin chain. (scielo.br)
  • 1 , 2 SCA is characterized by a variable clinical course and differences in response to medication, reflecting its complex pathophysiology and suggesting that it can be affected by modulator factors such as the haplotypes of the beta globin chain or fetal hemoglobin (Hb F) levels. (scielo.br)
  • Impaired switching from fetal hemoglobin (HbF) to adult globin gene expression leads to hereditary persistence of fetal hemoglobin (HPFH) in adult life. (unina.it)
  • Fetal hemoglobin levels are regulated by complex mechanisms involving factors linked or not to the beta-globin gene locus. (unina.it)
  • A hemoglobin electrophoresis evaluation (HBELC / Hemoglobin Electrophoresis Cascade, Blood) is always indicated prior to beta globin gene sequencing because these conditions can be complex and protein data allows accurate and rapid classification of the patient phenotype. (mayocliniclabs.com)
  • Beta globin gene ( HBB ) sequencing can be used to identify hemoglobin variants and the most common beta thalassemia sequence variants, including beta plus and beta zero thalassemias. (mayocliniclabs.com)
  • Some hemoglobin disorders will not be detected by beta globin gene sequencing, such as large deletional alterations and crossover events. (mayocliniclabs.com)
  • The name hemoglobin is derived from the words heme and globin, reflecting the fact that each subunit of hemoglobin is a globular protein with an embedded heme group. (wikipedia.org)
  • Hemoglobin consists of protein subunits (the globin molecules), and these proteins, in turn, are folded chains of a large number of different amino acids called polypeptides. (wikipedia.org)
  • These conditions all have in common an imbalanced rate of production of the globin chains of adult hemoglobin, excess α chains in β - thalassemia and excess β chains in α - thalassemia. (mhmedical.com)
  • Human fetal globin gene expression is regulated by LYAR. (nih.gov)
  • We found that PRMT5 binding on the proximal γ-promoter was LYAR-dependent.We also found that LYAR repressed human fetal globin gene expression in both K562 cells and primary human adult erythroid progenitor cells.Thus, these data indicate that LYAR acts as a novel transcription factor that binds the γ-globin gene, and is essential for silencing the γ-globin gene. (nih.gov)
  • Here we discuss the significance of ACH formation, provide an overview of the proteins implicated in chromatin looping at the beta-globin locus, and evaluate the relationship between nuclear organization and beta-globin gene expression. (nih.gov)
  • A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure. (harvard.edu)
  • Bacterial globins are proteins possessing the classical globin fold and the highly conserved active site residues required for ligand-binding function. (springer.com)
  • Bacterial globins are classified into three major groups - myoglobin-like globins (two- or single-domain proteins), sensor globins, and truncated globins. (springer.com)
  • Globins are an ancient superfamily of diverse proteins (Vinogradov et al. (springer.com)
  • 2. The preparation as claimed in claim 1, comprising a material that comprises globin that is insoluble at physiological pH with globin that is soluble at physiological pH and, in smaller amounts, plasma proteins, especially albumin, coagulation factors and platelet factors. (freepatentsonline.com)
  • 15. A process for obtaining the preparation as claimed in claim 1, in which whole blood, preferably defrosted or hemolyzed whole blood, is treated in a medium that extracts or dissolves the haem but leaves the globin and the other constituents of proteinic nature in a substantially undissolved state, and then the pigmented medium is removed to yield the globin together with other blood proteins. (freepatentsonline.com)
  • The proteins are named globins, I learned later, reading Goldstrohm's thesis, because they're globular in shape. (psu.edu)
  • At first blush, these globin proteins look like each other," Hardison said. (psu.edu)
  • Class I bHLH proteins are important transcription factors whose binding sites are frequently clustered throughout the β-globin gene locus, suggesting their role in globin gene regulation. (umontreal.ca)
  • The F family comprises single domain globins and chimeric, -400aa proteins with C-terminal ferredoxin reductase-like domain. (uzh.ch)
  • The S family consists of single domain globins and chimeric proteins with variable (300-700aa) C-terminal domain(s)involved in chemotaxis and gene regulation. (uzh.ch)
  • Overall, the globin superfamily has displayed unsuspected versatility and extraordinary success in evolving from useful but dispensable proteins in a majority of prokaryotes, to ubiquitous indispensability in the crown eukaryotes. (uzh.ch)
  • Incubation of chicken reticulocytes at elevated temperatures (43 to 45 degrees C) resulted in a rapid change in the pattern of protein synthesis, characterized by the decreased synthesis of normal proteins, e.g., alpha and beta globin, and the preferential and increased synthesis of only one heat shock protein, HSP70. (asm.org)
  • This could be confered by ~22-nucleotide long microRNAs that associate with argonaute proteins to specifically target γ-globin mRNAs and inhibit protein expression. (uzh.ch)
  • Aims Fusion proteins of unequal recombination events at the β-globin locus have pathological effect. (bmj.com)
  • The haemoglobin (Hb) variants of type Lepore are fusion proteins characterised by β-like globin chains with a δ-globin ( HBD ) N-terminus and a β-globin ( HBB ) C-terminus, whereas reciprocal products of underlying crossover events hold a HBB N-terminus and HBD C-terminus instead. (bmj.com)
  • Finally, Hb Parchman contains a β-like globin chain with a central HBB fragment and HBD -derived N-termini and C-termini, whereas reciprocal hybrid proteins are as yet unknown. (bmj.com)
  • In the past they used to be primarily characterized as oxygen transport/storage proteins, but since the discovery of new members of the globin family like neuroglobin and cytoglobin, more diverse and complex functions have been assigned to this heterogeneous family. (ugent.be)
  • Fast and accurate computation of protein stability is increasingly important for e.g. protein engineering and protein misfolding diseases, but no consensus methods exist for important proteins such as globins, and performance may depend on the type of structural input given. (dtu.dk)
  • The 7TM domains of both proteins appeared very similar, but the globin domain of the A. suum receptor surprisingly seemed to lack several helices, suggesting a novel truncated globin fold. (ugent.be)
  • Globins are small heme proteins that are present in almost all extant organisms. (ijbs.com)
  • Globins (Gbs) are small heme proteins that have been found in all kingdoms of life in a wide range of different species [ 1 - 3 ]. (ijbs.com)
  • The chimeric FHb proteins possess an N-terminal globin domain and a C-terminal FAD- and NAD(P)H-binding reductase domain. (ijbs.com)
  • Delayed globin synthesis leads to excess heme and the macrocytic anemia of Diamond Blackfan anemia and del(5q) myelodysplastic syndrome. (harvard.edu)
  • therefore, heme synthesis must precede globin synthesis. (jci.org)
  • Unbalanced production of α-globin in the presence of defective synthesis of β-globin is the primary mechanism for anaemia in β-thalassaemia. (nature.com)
  • Heat shock-induced translational control of HSP70 and globin synthesis in chicken reticulocytes. (asm.org)
  • Upon return to control temperatures (37 degrees C), heat-shocked reticulocytes continued to synthesize HSP70 at elevated levels whereas globin synthesis continued to be repressed. (asm.org)
  • report that ribosomal deficiencies in individuals with either DBA or Del(5q) MDS lead to insufficient globin protein synthesis but normal heme synthesis, which results in excess heme and reactive oxygen species in early erythroid precursors and proerythroblast cell death. (sciencemag.org)
  • We show that globin translation initiates slowly, whereas heme synthesis proceeds normally. (sciencemag.org)
  • By crossing huα+/0, muα++/−− mice, we were able to generate mice entirely dependent on huα-globin synthesis. (deepdyve.com)
  • The myriad manifestations of thalassemia result from the imbalanced synthesis of α-like and non-α-like globin chains and from the accumulation of unpaired counterpart. (alliedacademies.org)
  • Nevertheless, they fail to direct alpha globin synthesis in an interspecific hybrid containing the abnormal (alpha alpha)RA chromosome. (ox.ac.uk)
  • The beta globin locus has long served as a major paradigm for studies of eukaryotic gene regulation and transcription. (hstalks.com)
  • B ) The TATA box mutation abolishes transcription of the γ-globin gene. (pnas.org)
  • C ) In vitro γ-globin gene transcription is inhibited by addition of the TATA box oligonucleotide (lane 2) into the assay system but not by poly(dI-dC) or the oligonucleotide with mutated TATA box. (pnas.org)
  • Transcription initiation site of the TATA box-mutated γ-globin gene. (pnas.org)
  • For the first time, we found that in other hematopoietic lineages, human β-globin locus is in active chromatin and interacts with transcription factors involved in repression. (umontreal.ca)
  • Gordon, C & Perkins, AC 1999, ' A transcription factor complex at the beta-globin CCAAT site involving members of the C/EBP family of B-zip protein may be involved in haemoglobin switching ', 11th Lorne Cancer Conference, Victoria, Australia, 11/02/99 - 14/02/99 pp. 1006 - 1006. (monash.edu)
  • The Oct-1 transcription factor is involved in the transcriptional regulation of the γ-globin gene. (wayne.edu)
  • We have studied the possibility of inducing γ-globin gene expression using decoy oligonucleotides that target the Oct-1 transcription factor consensus sequence. (wayne.edu)
  • The results of our immunoprecipitation (IP) studies revealed that the treatment of K562 cells with the Oct-1 decoy oligonucleotide significantly reduced the level of the endogenous γ-globin gene promoter region DNA co-precipitated with the Oct-1 transcription factor. (wayne.edu)
  • His team sought to understand globin gene expression, studying both cis- and trans-acting components that regulate transcription of the gene. (wikipedia.org)
  • Variation of postnatal γ globin expression and HbF production in these patients was thought to be one of the main genetic factors responsible for clinical heterogeneity found in Hb E/ β thalassemia by reducing globin imbalance and ameliorating ineffective erythropoiesis. (hindawi.com)
  • In a recent study using a more refined SNP analysis of the β globin gene cluster in HbE/ β thalassemia has shown that there was no other variant elsewhere which has a comparable level of association with that of Xmn I site and the T allele ( Xmn I, +) was almost always in cis with the HbE alleles [ 10 ]. (hindawi.com)
  • A thalassemia mutation of the human β-globin gene as a model system. (bloodjournal.org)
  • A mutation of the human β-globin gene, which is a rare cause of β-positive thalassemia and which was first observed in a patient with homozygous β-thalassemia intermedia. (bloodjournal.org)
  • We describe a patient originating from Ghana who had combined heterozygous -α 4.2 thalassemia, ααα anti3.7 triplication, the common δ globin variant HbA 2 ' and a new 65 bp duplication/insertion in exon II of the β globin gene causing β 0 -thalassemia. (haematologica.org)
  • Baird M, Driscoll C, Schreiner H, Sciarratta GV, Sansone GN, Niazi G, Ramirez F, Bank A (1981) A nucleotide change at a splice junction in the human β-globin gene is associated with β°-thalassemia. (springer.com)
  • Flavell RA, Bernardo R (1979) The structure of the human β-globin gene in b-thalassemia. (springer.com)
  • Kan Y, Lee KY, Furbetta M, Angius A, Cao A (1980) Polymorphism of DNA sequence in the β-globin gene region: Application to prenatal diagnosis of β°-thalassemia in Sardinia. (springer.com)
  • Orkin SH, Old JM, Weatherall DJ, Nathan DG (1979) Partial deletion of β-globin gene DNA in certain patients with β°-thalassemia. (springer.com)
  • This test ca be used to detect the presence of absence of large deletions in the HBA1 or HBA2 gene in patients or their family members suspected of having alpha thalassemia or who are carriers of alpha globin deletions. (specialtylabs.com)
  • In this study, we compare the expression of the human β-globin gene from either the HS2/HS3 β-globin LCR or the HS40 regulatory element from the α-globin locus in the context of foamy virus (FV) vectors for the genetic correction of β-thalassemia. (ovid.com)
  • Both regulatory elements expressed comparable levels of human β-globin in a murine erythroleukemic line, whereas in murine hematopoietic stem cells the HS40.β vector proved more efficient in β-globin expression and correction of the β-thalassemia phenotype. (ovid.com)
  • Our data suggest that FV vectors with the α-globin HS40 element can be used as alternative but equally efficient vehicles for human β-globin gene expression for the genetic correction of β-thalassemia. (ovid.com)
  • This animal model should be valuable for studying the mechanisms regulating huα-globin production and for development of therapeutic strategies for β-thalassemia based on downregulation of α-globin expression. (deepdyve.com)
  • To search for factors putatively involved in gamma-globin gene expression, we examined the reticulocyte transcriptome of three siblings who had different HbF levels and different degrees of beta-thalassemia severity although they had the same alpha- and beta-globin gene cluster genotypes. (unina.it)
  • This is a second-tier evaluation of beta thalassemia minor, intermedia, and major, as well as beta globin variant identification. (mayocliniclabs.com)
  • A common mutation causing thalassemia in Mediterranean populations is an amber (UAG) nonsense mutation at the 39th codon of the human β globin gene, the β-39 mutation. (yale.edu)
  • Takara's Human Beta-globin Control Primer Set contains a set of PCR primers that recognizes the human beta-globin gene at chromosome 11. (clontech.com)
  • Location of the two adult α-globin paralogs, HBA-T1 and HBA-T2, on chromosome 11 (top). (genetics.org)
  • Location of the two adult β-globin paralogs, HBB-T1 and HBB-T2, on chromosome 7 (bottom). (genetics.org)
  • To explore the role of cis -regulatory sequences within the β globin gene cluster at chromosome 11 on human γ globin gene expression related to Hb E allele, we analyze baseline hematological data and Hb F values together with β globin haplotypes in homozygous Hb E. Patients and Methods . (hindawi.com)
  • Ioannou, Panayiotis 2005-11-11 00:00:00 A 191-kb human bacterial artificial chromosome (BAC) containing the human α-globin genomic locus was used to generate transgenic mice that express, exclusively, human α-globin (huα-globin). (deepdyve.com)
  • β-globin gene cluster haplotypes in sickle cell patients from Panamá. (biomedsearch.com)
  • OBJECTIVE: To analyze the frequency of the haplotypes of β-globin gene cluster in randomly selected patients with sickle cell disease (SCD), attended in the Children's Hospital of Panama. (biomedsearch.com)
  • Surprisingly high levels of nucleotide polymorphism at the two β-globin paralogs were attributable to the segregation of two highly divergent haplotypes, Hbb s (which carries two identical β-globin paralogs) and Hbb d (which carries two functionally divergent β-globin paralogs). (genetics.org)
  • 80 individuals with molecularly confirmed homozygous Hb E were analyzed for the β globin haplotypes and Xmn I polymorphism using PCR-RFLPs. (hindawi.com)
  • To further explore the role of cis -acting sequences on Hb F production under the less hematopoietic stress and globin chain imbalance in Hb E disorders, we analyzed 7 known single nucleotide polymorphisms within the 50 kb of the β globin gene cluster to construct Hb E-linked β globin haplotypes together with Xmn I polymorphism. (hindawi.com)
  • The β globin haplotypes of Hb E have been characterized previously in Thailand and within the region of Southeast Asia but they were principally utilized to identify origin, spread, and anthropology of different ethnic groups found with Hb E [ 11 - 13 ]. (hindawi.com)
  • Clinical genetic data accumulated over three decades have clearly demonstrated that direct suppression of α-globin and induction of γ-globin are effective in reducing the globin chain imbalance in erythroid cells hence improving the clinical outcome of patients with β-thalassaemia. (nature.com)
  • We show that vorinostat directly reduces the production of α-globin whilst inducing the expression of γ-globin in human erythroid cells without perturbing erythroid proliferation, viability, differentiation or global gene expression. (nature.com)
  • We previously performed a small molecule screen using Fluidigm high throughput qPCR platform to identify compounds that alter globin gene expression in human erythroid cells to identify compounds that produce favourable effects for β-thalassaemia. (nature.com)
  • Tuan D, Biro PA, De Riel JK, Lazarus H, Forget BG (1979) Restriction endonuclease mapping of the human γ-globin gene loci. (springer.com)
  • Altogether, clarifies Goldstrohm, humans can make six different hemoglobins-three during the embryo stage, one as a fetus, and two as adults-using the different forms of globins. (psu.edu)
  • Here's a diagram showing the pseudogene in the β-globin gene cluster in humans and chimps. (blogspot.com)
  • Gas chromatographic-mass spectrometric determination of benzo[a]pyrene and chrysene diol epoxide globin adducts in humans. (aacrjournals.org)
  • The results of this study demonstrate the feasibility of the GC-NICI-MS-SIM method for measurement of BPDE globin adducts in humans. (aacrjournals.org)
  • In humans, the β-globin gene domain is located in the GC-depleted isochore and contains multiple nuclear matrix attachment regions. (deepdyve.com)
  • The globin superfamily can be divided into three lineages, namely the S, F, and T globins, which belong to two structural classes [ 5 - 7 ]. (ijbs.com)
  • Two so-called beta-like globin chains and two alpha-like globin chains. (hstalks.com)
  • In each tetramer, the four globin chains are held together by noncovalent attractions. (hstalks.com)
  • This unbalanced production of α- and β-like globin chains leads to precipitation of free α-globin chains in red blood cells (RBC) and their precursors to cause haemolysis and ineffective erythropoiesis which are considered as the primary pathophysiological mechanism for the anaemia in thalassaemia 11 . (nature.com)
  • This paper describes the use of high-performance capillary electrophoresis for the separation of globin chains. (nus.edu.sg)
  • like globin chains and from the accumulation of unpaired counterpart. (alliedacademies.org)
  • Unpaired globin chains are unstable: they form intracellular aggregates which are insoluble and precipitate causing decreased deformability, membrane damage and selective removal of the damaged cell. (alliedacademies.org)
  • The β-thalassemias are characterized by a quantitative deficiency of β-globin chains underlaid by a striking heterogeneity of molecular defects. (alliedacademies.org)
  • Through erythroid development, the γ globin expression was regulated by interactions between cis -acting sequences within the β globin cluster and trans -acting factors such as BCL-11A, cMYB, and TOX [ 1 , 6 - 8 ]. (hindawi.com)
  • Draft sequences of the Atlantic cod genome enabled us to determine the genomic organization of the globin repertoire in this marine species that copes with fluctuating environments of the temperate and Arctic regions. (bibsys.no)
  • We transfected mouse erythroleukemia cells with a 15 kbp plasmid containing a lac operator repeat plus β-globin regulatory sequences driving a β-galactosidase reporter gene. (biologists.org)
  • β-Globin locus control region (LCR) sequences have been widely used for the regulated expression of the human β-globin gene in therapeutic viral vectors. (ovid.com)
  • Conclusion Hb Palencia contains the first globin variant with internal HBD sequences and HBB -derived N-terminal and C-terminal and regulatory sequences. (bmj.com)
  • It seems probable that previously unidentified positive regulatory sequences analogous to those detected in a corresponding position of the human beta globin cluster are removed by this deletion. (ox.ac.uk)
  • Total RNA from yolk sac or adult blood was hybridized with a 32 P-labeled RNA probe spanning exon 1 to −382 promoter of the γ-globin gene. (pnas.org)
  • And even among the beta-globin gene family, we have embryonic, fetal, and adult forms. (psu.edu)
  • Adult White Leghorn chickens were rendered anemic by injection with 1-acetyl-2-phenylhydrazine and then treated with parenteral 5-azacytidine, and levels of embryonic globin RNA in circulating reticulocytes were measured. (pnas.org)
  • Numerous studies have been carried out in humanised mice models and have shown that genetic manipulations of the locus could activate adult β-globin expression. (gla.ac.uk)
  • Due to consistent differences in O 2 -binding properties between HbD and the major adult-expressed Hb isoform, HbA (which incorporates products of the α A -globin gene), recurrent losses of α D -globin contribute to among-species variation in blood-O 2 affinity. (unl.edu)
  • The Dominant Control Region (DCR) of the human beta-globin gene locus consists of four strong hypersensitive sites (HSS) upstream of the epsilon-globin gene. (nih.gov)
  • They include epsilon-globin, gamma-globin, delta-globin and beta-globin. (curehunter.com)
  • A. Two IEs (yellow) bounded by loxP elements (stippled black) were inserted into the γ A promoter region of a YAC containing the human β-globin locus , and this was used to generate transgenic mice that were then crossed with two different cre-expressing lines. (nih.gov)
  • Recruitment of TBP, TFIIB, and Pol II in the transgenic mice carrying the TATA box-mutated γ-globin gene. (pnas.org)
  • Hemizygous transgenic mice carrying the huα-globin locus on a heterozygous knockout background (huα+/0, muα++/−−) demonstrated complementation of most hematologic parameters. (deepdyve.com)
  • Our studies demonstrate that the huα-globin locus in the 191-kb transgene contains all the necessary elements for the regulated expression of huα-globin in transgenic mice. (deepdyve.com)
  • Investigators are currently working on optimizing manufacturing of their vector, which is believed to achieve better expression of β-globin on a per-copy basis, and therefore the potential for superior clinical results, than other vectors utilized in treatments under development elsewhere. (mskcc.org)
  • Fine tuning of globin gene expression by DNA methylation. (nih.gov)
  • Expression patterns in the globin gene cluster are subject to developmental regulation in vivo. (nih.gov)
  • We show that a 225 bp fragment is sufficient to direct high levels of expression of the human beta-globin gene which is copy number dependent and integration site independent. (nih.gov)
  • The significance of these results for the regulation of globin gene expression is discussed. (nih.gov)
  • The in vitro γ-globin gene expression depends upon an intact TATA box and recruitment of TBP. (pnas.org)
  • We further show that vorinostat exhibits these synergistic beneficial effects in globin gene expression at nanomolar concentrations without perturbing erythroid expansion, viability, differentiation or the transcriptome. (nature.com)
  • Using human β-globin locus as a model, we investigated how the transcriptional machinery is set and regulated during erythropoiesis and how it impacts globally on gene expression. (umontreal.ca)
  • The scheme provides an overview on the expression and evolution of fish globins. (biologists.org)
  • Expression of D. rerio globins at different oxygen levels. (biologists.org)
  • Rate of expression of D. rerio globin expression under hypoxia. (biologists.org)
  • The cis-regulation of γ globin gene expression might not be apparent under a milder condition with lesser globin imbalance such as homozygous Hb E. (hindawi.com)
  • The effects of WDR5 knockdown on γ-globin gene expression were determined. (haematologica.org)
  • Results We found that WDR5 interacted with protein arginine methyltransferase 5 (PRMT5), a known repressor of γ-globin gene expression, and was essential for generating tri-methylated H3K4 (H3K4me3) at the γ-globin promoter in K562 cells. (haematologica.org)
  • Enforced expression of WDR5 in K562 cells reduced γ-globin gene expression, whereas knockdown of WDR5 increased γ-globin gene expression in both K562 cells and primary human bone marrow erythroid progenitor cells. (haematologica.org)
  • In human BMC, levels of WDR5 were highly enriched on the γ-promoter relative to levels on other globin promoters and compared to the γ-promoter in cord blood erythroid progenitors, suggesting that WDR5 is important in the developmental globin gene expression program. (haematologica.org)
  • H3K4me3 induced at the γ-globin promoter by WDR5 may result in the recruitment of the ING2-associated HDAC1 component and consequent silencing of γ-globin gene expression. (haematologica.org)
  • The plasticity of Atlantic cod to variable environmental conditions probably involves the expression of multiple globins with potentially different properties. (bibsys.no)
  • Several studies have indicated that expression of the HbF subunit γ-globin might be regulated post-transcriptionally. (uzh.ch)
  • Moreover, luciferase reporter assays showed that microRNA-96 negatively regulates expression of γ-globin in HEK293 cells, which depends on a seedless but highly complementary target site located within the coding sequence of γ-globin. (uzh.ch)
  • Based on these results we conclude that microRNA-96 directly suppresses γ-globin expression and thus contributes to HbF regulation. (uzh.ch)
  • In addition, in an ex vivo assay using CD34+ cells from thalassemic patients, both vectors achieved significant human β-globin expression and restoration of the thalassemic phenotype as evidenced by enhanced erythropoiesis and decreased apoptosis. (ovid.com)
  • Human γ-globin gene expression is developmentally regulated, and is gradually silenced after birth. (nih.gov)
  • This is consistent with the putative role of LYAR as a repressor of γ-globin expression. (nih.gov)
  • Increasing the expression of the γ-globin gene has great benefits in reducing complications associated with these diseases. (wayne.edu)
  • The study also confirmed the presence of a 150-base pair Alu insertion element and a 1.8-kb deletion in the g 1 -globin pseudogene in A. fusca , features found previously in the remaining three species. (scielo.br)
  • Leicester Research Archive: Processes of copy-number change in human DNA: the dynamics of {alpha}-globin gene deletion. (le.ac.uk)
  • Processes of copy-number change in human DNA: the dynamics of {alpha}-globin gene deletion. (le.ac.uk)
  • Finally, direct knowledge of germ-line deletion rates can give insights into the fitness of individuals with these alpha-globin gene deletions, providing a new approach to investigating historical levels of selection operating in human populations. (le.ac.uk)
  • A silent deletion in the beta-globin gene cluster. (ox.ac.uk)
  • A survey of the gamma-globin gene region of over 1000 normal individuals revealed a novel 2.5 kb deletion which removes the 5' end of the A gamma-globin gene. (ox.ac.uk)
  • Unusually, this deletion in the beta-globin gene cluster is not associated with increased fetal haemoglobin production. (ox.ac.uk)
  • Short in-Frame Insertions/Deletions in the Coding Sequence of the α-Globin Gene. (inserm.fr)
  • In search to visualize and measure these dynamic changes in chromatin structure of the β-globin locus, we used a 3D DNA-FISH method in combination with 3D image acquisition to volume render fluorescent signals into 3D objects. (biologists.org)
  • article{3239049, abstract = {Globins occur in all kingdoms of life where they fulfill a wide variety of functions. (ugent.be)
  • The pathophysiology of the thalassemias can be traced to the deleterious effects of the globin-chain subunits that are produced in excess. (mhmedical.com)
  • Poole RK, Hughes MN (2000) New functions for the ancient globin family: bacterial responses to nitric oxide and nitrosative stress. (springer.com)
  • There is also evidence that HU can act as a nitric oxide donor and increase cyclic guanosine monophosphate (cGMP) levels, which upregulate the translation of the γ globin. (scielo.br)
  • In its ferrous deoxy form, GLB-33 GD is capable of reversibly binding O-2 with a very high affinity and of reducing nitrite to nitric oxide faster than other globins. (ugent.be)
  • The molecule also carries the important regulatory molecule nitric oxide bound to a globin protein thiol group, releasing it at the same time as oxygen. (wikipedia.org)
  • Gene Turnover in the Avian Globin Gene Families and Evolutionary Chan" by Juan C. Opazo, Federico G. Hoffmann et al. (unl.edu)
  • Frey AD, Shepherd M, Jokipii-Lukkari S, Haggman H, Kallio PT (2011) The single-domain globin of Vitreoscilla: augmentation of aerobic metabolism for biotechnological applications. (springer.com)
  • Shepherd M, Barynin V, Lu CY, Bernhardt PV, Wu GH et al (2010) The single-domain globin from the pathogenic bacterium Campylobacter jejuni . (springer.com)
  • Moreover, a single-domain globin (SDFgb) of Hartmannella vermiformis , as well as two truncated hemoglobins (trHbs) of Acanthamoeba castellanii were identified. (ijbs.com)
  • Role of LYAR in developmental globin gene silencing. (nih.gov)
  • An attempt to increase embryonic globin RNA induction by treatment with parenteral sodium butyrate after 7 days of 5-azacytidine administration resulted in a 5- to 10-fold increase in the level of embryonic globin RNA. (pnas.org)
  • All bacterial Hbs belong to one of three families: the flavohemoglobins (F) and sensor (S) globins, that display the canonical 3/3 α-helical fold characteristic of the metazoan Hbs, and the 2/2 ("truncated") Hbs (T), that exhibit a shortened 2/2 α-helical fold. (uzh.ch)
  • The members of the F and S lineages possess the typical globin fold, i.e. a 3-over-3 (3/3) α-helical fold consisting of seven or eight α-helices, designated A through H [ 8 ]. (ijbs.com)
  • The HBBP1 gene also has the most regulatory associations with active and open chromatin within the entire β-globin cluster and its transcripts are expressed in at least 251 different human cell and/or tissue types. (blogspot.com)
  • We hypothesize that the fusion of the three chordate linkage groups 3, 15 and 17 more than 800 MYA led to the ancestral vertebrate globin cluster during a geological period of increased atmospheric oxygen content. (bibsys.no)
  • Antonarakis SE, Boehm CD, Giardina PJV, Kazazian HH Jr (1982) Nonrandom association of polymorphic restriction sites in the β-globin gene cluster. (springer.com)
  • We surveyed nucleotide polymorphism in two closely linked α-globin paralogs and two closely linked β-globin paralogs to test whether patterns of variation are consistent with a model of long-term balancing selection. (genetics.org)
  • Levels of nucleotide polymorphism and linkage disequilibrium at the two β-globin paralogs suggest a complex history of diversity-enhancing selection that may be responsible for long-term maintenance of alternative protein alleles. (genetics.org)
  • Kan YM, Dozy AM (1978) Polymorphism of DNA sequence adjacent to human β-globin structural gene: Relationship to sickle mutation. (springer.com)
  • Human genomic DNA was amplified by using a pair of primers covering the TATA box of the γ-globin promoter. (pnas.org)
  • Genomic structure of the α- and β-globin gene families of M. musculus . (genetics.org)
  • A comparative genomic analysis of 52 bird species revealed that the size and membership composition of the α- and β-globin gene families have remained remarkably constant during approximately 100 My of avian evolution. (unl.edu)
  • In the present study we have analyzed whole genomic data from C. briggsae, C. remanei, Pristionchus pacificus and Brugia malayi and EST data from several other nematode species to study the evolutionary history of the nematode globin gene family. (wayne.edu)
  • The WD40-repeat protein, WDR5, is an essential component of the MLL complex that induces histone H3 K4 methylation, but the role of WDR5 in human globin gene regulation has not yet been established. (haematologica.org)
  • Design and Methods To study the role of WDR5 in human globin gene regulation, we performed knockdown experiments in both K562 cells and primary human bone marrow erythroid progenitor cells (BMC). (haematologica.org)
  • A very small but detectable amount of correctly initiated embryonic p-type globin RNA was detected in reticulocytes from birds treated with 5-azacytidine, while none was detected in reticulocytes from those receiving only phenylhydrazine or phenylhydrazine plus 1-beta-D-arabinofuranosylcytosine (cytosine arabinonucleoside). (pnas.org)
  • Most interspecific variation in gene content is attributable to multiple independent inactivations of the α D -globin gene, which encodes the α-chain subunit of a functionally distinct Hb isoform (HbD) that is expressed in both embryonic and definitive erythrocytes. (unl.edu)
  • Consistent with this, both histone H3 and H4 acetylation at the γ-globin promoter were increased, while histone H4R3 and H3K9 methylation were decreased, in WDR5 knockdown cells compared to controls. (haematologica.org)