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
A 350-bp segment of DNA associated with an erythroid-specific DNase I-hypersensitive site (HS-40), upstream of the alpha-globin gene cluster, has been identified as the major tissue-specific regulator of the alpha-globin genes. However, this element does not direct copy number-dependent or developmentally stable expression of the human genes in transgenic mice. To determine whether additional upstream hypersensitive sites could provide more complete regulation of alpha gene expression we have studied 17 lines of transgenic mice bearing various DNA fragments containing HSs -33, -10, -8, and -4, in addition to HS -40. Position-independent, high-level expression of the human zeta- and alpha-globin genes was consistently observed in embryonic erythroid cells. However, the additional HSs did not confer copy-number dependence, alter the level of expression, or prevent the variable down-regulation of expression in adults. These results suggest that the region upstream of the human alpha-globin genes is not
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
We have set up an experimental system to map the primary transcription unit of the human alpha 2 globin gene. The duplicated human alpha globin genes (alpha 2-alpha 1) were linked to the alpha globin locus Positive Regulatory Element (PRE) and stably transfected into murine erythroleukaemia cells. We then developed a quantitative reverse transcriptase, polymerase chain reaction assay to map alpha 2 primary transcripts using primer pairs derived from different parts of the alpha 2 globin gene and its 3 flanking region. This approach has revealed the presence of steady state nuclear RNA past the poly(A) site of the alpha 2 globin gene at approximately 40% of the level of unspliced intron transcript. Furthermore, these 3 flanking transcripts diminish 500 bp into the 3 flanking region, identifying this part of the alpha 2 globin gene as the principal region of termination of transcription.
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 ...
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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 ...
TY - JOUR. T1 - In Silico Analysis of the Effects of Point Mutations on α-Globin. T2 - Implications for α-Thalassemia. AU - Horri-Naceur, Agathe. AU - Timson, David J.. N1 - This is an Accepted Manuscript of an article published by Taylor & Francis in Hemoglobin on 18/05/2020, available online: http://www.tandfonline.com/10.1080/03630269.2020.1739067. PY - 2020/5/18. Y1 - 2020/5/18. N2 - Hemoglobinopathies are inherited diseases that impair the structure and function of the oxygen-carrying pigment hemoglobin (Hb). Adult Hb consists of two α and two β subunits. α-Thalassemia (α-thal) affects the genes that code for the α-globin chains, HBA1 and HBA2. Mutations can result in asymptomatic, mild or severe outcomes depending on several factors, such as mutation type, number of mutations and the location at which they occur. PredictSNP was used to estimate whether every possible single nucleotide polymorphism (SNP) would have a neutral or deleterious effect on the protein. These results were ...
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 …
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.
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.. ...
The polymerase chain reaction (PCR) is one of the most powerful techniques used in molecular biology . With this method, a few ng of DNA can be amplified millions of times in a test tube in a few hours. The PCR has been used extensively in studies of gene structure and function. The method is also becoming increasingly important in DNA typing procedures such as DNA fingerprinting and in the identification and characterization of mutations that cause human diseases. This exercise is designed to illustrate the PCR in the teaching laboratory. In the experiment, students use PCR to amplify a rabbit ß-globin gene. The template for this reaction is a plasmid that contains this globin sequence. Following PCR amplification, the product of the reaction is analyzed on an agarose gel as shown on the below. The experiment was designed so that the PCR can be done manually provided that three standard water baths (45°C, 74°C, and 94°C) or three hot plates are available. The amplified globin DNA band can ...
The duplicated human embryonic alpha-like globin genes encode a 5 functional zeta (xi 2) gene and a highly homologous pseudogene (psi xi 1). We have identified chromosomes with a xi 2-xi 1 rather than a xi 2-psi xi 1 arrangement by genomic mapping and oligonucleotide analysis. The DNA sequence of a cloned downstream xi-like gene provides direct evidence for the conversion of a psi xi 1----xi 1 gene, by a xi 2 gene. We present data suggesting that this gene conversion, which removed the only identifiable inactivating mutation in the psi xi 1 gene, was an interchromosomal event. The xi 2-xi 1 arrangement is common in all eight populations studied representing a previously undescribed type of polymorphism between individuals. Stable mRNA transcripts from the converted gene are absent at 16-20 weeks of gestation when transcripts from the xi 2 gene are readily detectable.
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 ...
Alpha thalassemia is a hemoglobinopathy on account of decreased manufacturing of the α-globin protein from loss of as much as 4 α-globin genes, with one or two lacking in the trait phenotype. Individuals with sickle cell illness who co-inherit the loss of one or two α-globin genes have been recognized…. ...
Alpha thalassemia is a hemoglobinopathy on account of decreased manufacturing of the α-globin protein from loss of as much as 4 α-globin genes, with one or two lacking in the trait phenotype. Individuals with sickle cell illness who co-inherit the loss of one or two α-globin genes have been recognized…. ...
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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.
Following the successful isolation of graphene,1 the family of two-dimensional (2D) materials has attracted great attention. This family has a large variety of members including mono-atomic honeycomb structures (silicene,2 germanene3), transition metal dichalcogenides (MoS2,4 WS2,5 ReS2 (ref. 6)) and group III-V compounds (h-BN,7 h-AlN8,9). Recently, Yang et al. proposed a new class of highly stable planar hypercoordinated materials, such as hexacoordinated Ni2Ge,10 Cu2Ge,11 Cu2As,12 Au13 and Cu,14 which open up a new branch for the 2D materials. Those materials have attracted attention due to their structural and mechanical properties such as strong chemical bonding and in-plane stiffness. One of these novel materials is the monolayer Cu2Si15 with planar hexacoordinated Cu and Si motifs. It is a nonmagnetic metal with high stability stemming from the superposition of 4c-2e σ bonds extended within the 2D sheet. The metallicity of Cu2Si has been known, Feng et al. verified Dirac nodal line ...
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 ...
TY - JOUR. T1 - Penetration studies of blood globin gels. AU - Autio, Karin. AU - Lyytikäinen, Heikki. AU - Mälkki, Yrjö. AU - Kanko, Sirpa. PY - 1985. Y1 - 1985. N2 - Studies were made on the effect of temperature, pH and protein and salt concentration on the penetration force withstood by globin gels. The registered force increased with heating temperature (60 ‐ 95°C) and protein concentration (1.4 ‐ 5.0%). The gelation pH was dependent on both protein and salt concentration; the higher the protein or salt concentration the lower the gelation pH. At 3% protein concentration globin formed a gel around pH 5 ‐ 6. At 0.7% concentration and higher, the presence of salt weakened the gel strength, while the addition of plasma increased the gelation pH of salt‐containing globin gels. A substantially higher penetration force was measured for bovine globin gels than porcine globin gels. Further concentration and spray‐drying decreased the gel strength of globin gels. AB - Studies were made ...
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 ...
Beta-thalassemias and hemoglobinopathies are serious inherited blood diseases caused by abnormal or deficiency of beta A chains of hemoglobin, the protein in red blood cells which delivers oxygen throughout the body. The diseases are characterized by hemolytic anemia, organ damage, and early mortality. Increases in another type of (normal) hemoglobin, fetal globin (HbF), which is normally silenced in infancy, reduce the severity of both conditions. Even incremental augmentation of fetal globin is established to reduce red blood cell pathology, anemia, certain complications, and to improve survival.. This trial will evaluate an oral drug discovered in a high throughput screen, which increases fetal globin protein and messenger ribonucleic acid (mRNA) to high levels in anemic nonhuman primates and in transgenic mice. The study drug acts by suppressing 4 repressors of the fetal globin gene promoter in progenitor cells from thalassemia patients. The drug has been used for many years in a combination ...
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 of 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
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
TY - JOUR. T1 - Hemin induces neuroglobin expression in neural cells. AU - Zhu, Yonghua. AU - Sun, Yunjuan. AU - Jin, Kunlin. AU - Greenberg, David A.. PY - 2002/10/1. Y1 - 2002/10/1. N2 - Neuroglobin is a newly identified vertebrate globin that binds O2 and is expressed in cerebral neurons. We found recently that neuronal expression of neuroglobin is stimulated by hypoxia and ischemia and protects neurons from hypoxic injury. Here we report that, like hemoglobin and myoglobin, neuroglobin expression can also be induced by hemin. Induction was concentration dependent and time dependent, with maximal (about 4-fold) increases in neuroglobin mRNA and protein levels occurring with 50 μM hemin and at 8 to 24 hours. The inductive effect of hemin was attenuated by the protein kinase G inhibitor KT5823 and the soluble guanylate cyclase inhibitor LY83583, was mimicked by treatment with 8-bromo-cyclic guanosine 3′,5′-monophosphate, and was accompanied by a greater than 10-fold increase in cGMP ...
Isolation of fetal erythroid cells from maternal blood based on expression of erythropoietin receptors. Mol Hum Reprod, 3, 451-5.
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 duplicated human embryonic α-like globin genes encode a 5′ functional zeta (ζ2) gene and a highly homologous pseudogene (ψζ1). We have identified chromosomes with a ζ2-ζ1 rather than a ζ2-ψζ1 arrangement by genomic mapping and oligonucleotide analysis. The DNA sequence of a cloned downstream ζ-like gene provides direct evidence for the conversion of a ψζ1→ζ1 gene, by a ζ2 gene. We present data suggesting that this gene conversion, which removed the only identifiable inactivating mutation in the ψζ1 gene, was an interchromosomal event. The ζ2-ζ1 arrangement is common in all eight populations studied representing a previously undescribed type of polymorphism between individuals. Stable mRNA transcripts from the converted gene are absent at 16-20 weeks of gestation when transcripts from the ζ2 gene are readily detectable. © 1985.
The alpha globin gene cluster is far from static. It shows remarkable diversity within and among populations, both in gene number and the pattern of polymorphisms involving the HVRs. The deletions which have given rise to alpha o thalassemia appear to have resulted from rare genetic events and the affected chromosomes have been distributed among localized populations by selection. On the other hand, the deletions which have given rise to at least one of the alpha+ thalassemias seem to have occurred on multiple occasions in different populations. The genesis of this condition, the commonest single gene disorder, may reflect the concerted evolution of the alpha globin genes, and the alpha+ thalassemias may have arisen as a by-product of this evolutionary process. The existence of such a polymorphic gene family and the fact that its mutations are the commonest single gene disorders in man, provide us with a remarkable, natural model for studying population genetics at the molecular level. Further analysis
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 F006/9417
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
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.
Written by Neil Kurtzman , 4th March 2017 Sickle Cell Disease is a disorder of hemoglobin production secondary to an alteration in the hemoglobin gene on chromosome 11. Specifically, there is a single amino acid substitution in adult β A -globin (Glu6Val) stemming from a single base substitution (A→T) in the first exon of the human β A -globin gene. The abnormal nucleotide…. ...
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. ...
Analisa DNA merupakan pemeriksaan yang mengidentifikasi adanya mutasi gen thalasemia, yaitu untuk Thalassemia beta -gen globin beta di kromosom 11 dan untuk Thalassemia alpha -gen globin alpha di kromosom 16. ...
Eight globins are known to occur in vertebrates: androglobin, cytoglobin, globin E, globin X, globin Y, hemoglobin, myoglobin ... The globin fold is found in its namesake globin families as well as in phycocyanins. The globin fold was thus the first protein ... Globin E: a globin responsible for storing and delivering oxygen to the retina in birds Globin-coupled sensors: chimeric, with ... single-domain globins, and two types of chimeric globins, flavohaemoglobins and globin-coupled sensors. Bacteria have all three ...
This locus contains not only the beta globin gene but also delta, gamma-A, gamma-G, and epsilon globin. Expression of all of ... The human β-globin locus is composed of five genes located on a short region of chromosome 11, responsible for the creation of ... The order of the genes in the beta-globin cluster is: 5' - epsilon - gamma-G - gamma-A - delta - beta - 3'. The arrangement of ... Many CRMs have been mapped within the cluster of genes encoding β-like globins expressed in embryonic (HBE1), fetal (HBG1 and ...
... flanking region of the beta-globin gene. The CoTC core is highly conserved in the 3' UTR of other primate beta-globin genes. ... The Beta-globin co-transcriptional cleavage ribozyme (CotC ribozyme) was proposed to be an RNA enzyme known as a ribozyme. ... Page for Beta-globin co-transcriptional cleavage ribozyme at Rfam v t e (Orphaned articles from May 2016, All orphaned articles ... This process is also referred to as co-transcriptional cleavage (CoTC). The CoTC process in the human beta-globin gene was ...
... belongs to the globin superfamily of proteins, and as with other globins, consists of eight alpha helices connected ... Wu G, Wainwright LM, Poole RK (2003). Microbial globins. Advances in Microbial Physiology. Vol. 47. pp. 255-310. doi:10.1016/ ...
... 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 ... The hemoglobin subunit beta is coded by HBB gene which is on chromosome 11 . The amino acid sequences of the globin proteins in ...
"N-Baltimore.html". globin.bx.psu.edu. Retrieved 2017-03-30. "Medical Archives - Personal Paper Collections: The C. Lockard ... Disorders of globin and globulin proteins, Mutation). ...
These globin genes in the globin family are all well conserved and only differ by a small portion of the gene, indicating that ... The globin gene family is an elaborate network of genes consisting of alpha and beta globin genes including genes that are ... An example of a gene family that may have been created due to copy number variations is the globin gene family. ... Goodman M, Koop BF, Czelusniak J, Weiss ML (December 1984). "The eta-globin gene. Its long evolutionary history in the beta- ...
Table 1: α represents the presence of α-globin gene and- represents the deletion of α-globin gene. The chance of a fetus ... As a result, gamma chains will accumulate and form four gamma globins. These gamma globins bind to form hemoglobin Barts. It is ... three alpha globin gene deletions). Deletion of four alpha globin genes was previously felt to be incompatible with life, but ... As an embryo develops, it begins to produce alpha-globins at weeks 5-6 of development. When both of the HBA1 and HBA2 genes ...
... is a globin molecule ubiquitously expressed in all tissues and most notably utilized in marine mammals. It was ... Geuens E, Brouns I, Flamez D, Dewilde S, Timmermans JP, Moens L (Aug 2003). "A globin in the nucleus!". The Journal of ... Burmester T, Ebner B, Weich B, Hankeln T (Apr 2002). "Cytoglobin: a novel globin type ubiquitously expressed in vertebrate ... Burmester T, Ebner B, Weich B, Hankeln T (Apr 2002). "Cytoglobin: a novel globin type ubiquitously expressed in vertebrate ...
"Regulation of Globin Gene Expression". {{cite journal}}: Cite journal requires ,journal= (help) "World Renowned Geneticist ... 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 ...
Banerji J, Rusconi S, Schaffner W (December 1981). "Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences ... Evans T, Felsenfeld G, Reitman M (1990). "Control of globin gene transcription". Annual Review of Cell Biology. 6: 95-124. doi: ... high-level expression of the human beta-globin gene in transgenic mice". Cell. 51 (6): 975-85. doi:10.1016/0092-8674(87)90584-8 ...
These globins reside inside a cell, much like the vertebrate Hb. Multi-subunit Hbs. These globins form complexes and work ... These globins form complexes, work outside a cell, and have multiple globin domains per peptide chain. Erythrocruorin and ... The isolation of the globin gene from plant root cells has suggested that the globin genes that were inherited from a common ... Globin enjoys a large biological distribution, not only occurring among more than 9 different phyla of animals but occurring in ...
Weatherall, D. J. (2015). "The Thalassemias: Disorders of Globin Synthesis". Williams Hematology (9e ed.). McGraw Hill ...
The epsilon globin gene (HBE) is normally expressed in the embryonic yolk sac: two epsilon chains together with two zeta chains ... Tuan D, Solomon W, Li Q, London IM (1985). "The "beta-like-globin" gene domain in human erythroid cells". Proc. Natl. Acad. Sci ... The five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5' - epsilon - gamma- ... 1977). "Human beta-globin messenger RNA. I. Nucleotide sequences derived from complementary RNA". J. Biol. Chem. 252 (14): 5019 ...
Villeponteau, B., Landes, G.M., Pankratz, M.J., and Martinson, H.G. (1982). The chicken beta globin gene region. Delineation of ... Lois, R., Freeman, L., Villeponteau, B., and Martinson, H.G. (1990). Active beta-globin gene transcription occurs in methylated ... Villeponteau, B., and Martinson, H.G. (1981). Isolation and characterization of the complete chicken beta-globin gene region: ... where he carried out genomic cloning of the B-globin gene cluster in Chickens.... He continued in the same department for six ...
The technology is based on delivery of a lentiviral vector carrying both the human β-globin gene and an ankyrin insulator to ... This test is used to investigate deletions and mutations in the alpha- and beta-globin-producing genes. Family studies can be ... Mutations are characterized as (βo) if they prevent any formation of β globin chains, mutations are characterized as (β+) if ... Most often, mutations occur in the promoter regions preceding the beta-globin genes. Less often, abnormal splice variants are ...
... zeta globins) and two ε globins (epsilon globins) (ζ2ε2) Hb Gower-2, composed of two alpha globins and two epsilon globins ( ... The severity of alpha and beta thalassemia depends on how many of the four genes for alpha globin or two genes for beta globin ... HbF induction is an attempt to reactivate fetal globin gene transcription. Efforts involve trying to disrupt the fetal globin ... α2ε2) Hb Portland, composed of two zeta globins and two gamma globins (ζ2γ2) Fetal Hb (Hb F) is produced from approximately ...
Freitas, Tracey Allen K.; Saito, Jennifer A.; Wan, Xuehua; Hou, Shaobin; Alam, Maqsudul (2008), "Protoglobin and Globin-coupled ... Synteny and Collinearity in Plant Genomes (2008). Protoglobin and globin-coupled sensors (2008). "About Professor Maqsudul Alam ...
The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains ... 1979). "Human T gamma globin chain is a variant of A gamma chain (A gamma Sardinia)". Proc. Natl. Acad. Sci. U.S.A. 76 (7): ... Fucharoen S, Shimizu K, Fukumaki Y (1990). "A novel C-T transition within the distal CCAAT motif of the G gamma-globin gene in ... 1977). "Human beta-globin messenger RNA. I. Nucleotide sequences derived from complementary RNA". J. Biol. Chem. 252 (14): 5019 ...
Expression of beta globin and the neighbouring globins in the β-globin locus is controlled by single locus control region (LCR ... Hemoglobin subunit beta (beta globin, β-globin, haemoglobin beta, hemoglobin beta) is a globin protein, coded for by the HBB ... The mutant alleles are subdivided into two groups: β0, in which no functional β-globin is made, and β+, in which a small amount ... The order of the genes in the beta-globin cluster is 5' - epsilon - gamma-G - gamma-A - delta - beta - 3'. HBB interacts with ...
... while alpha-globin is produced throughout fetal and adult life. The zeta-globin gene is a member of the human alpha-globin gene ... Zeta-globin is an alpha-like hemoglobin. The zeta-globin polypeptide is synthesized in the yolk sac of the early embryo, ... Lau ET, Kwok YK, Chui DH, Wong HS, Luo HY, Tang MH (July 2001). "Embryonic and fetal globins are expressed in adult erythroid ... Proudfoot NJ, Gil A, Maniatis T (December 1982). "The structure of the human zeta-globin gene and a closely linked, nearly ...
... is a member of the vertebrate globin family involved in cellular oxygen homeostasis and reactive oxygen/nitrogen ... It is of ancient evolutionary origin, and is homologous to nerve globins of invertebrates. Recent research confirmed the ... Burmester T, Weich B, Reinhardt S, Hankeln T (September 2000). "A vertebrate globin expressed in the brain". Nature. 407 (6803 ... science.gov, Neuroglobins, Pivotal Proteins Associated with Emerging Neural Systems and Precursors of Metazoan Globin Diversity ...
In 1979, his research group isolated the gene for epsilon-globin (HBE1), a component of human embryonic hemoglobin. He was one ... Proudfoot, NJ; Baralle, FE (November 1979). "Molecular cloning of human epsilon-globin gene". Proceedings of the National ... Tito published the sequence of the messenger RNA coding for beta-globin, the first complete primary structure of a eukaryotic ... "The Structure and evolution of the human b-globin gene family" "TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral ...
Flavell, R. A. (1983). "The globin genes of rabbit and man. The eighteenth Colworth medal lecture". Biochemical Society ...
Cocca, E (1997). "Do the hemoglobinless icefishes have globin genes?". Comp. Biochem. Physiol. A. 118 (4): 1027-1030. doi: ...
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 ...
... and his inquisitive and mischievous friend Globin. They carry oxygen bubbles or carbon dioxide bubbles in a back pouch, ... Plasmus and Globina for Hemo and Globin, Corpo for Jumbo; Toxicus, Germus and Infectius for the bacterium characters; Virulus ...
These globins dramatically improve the concentration of molecular oxygen that can be carried in the biological fluids of ... Examples of such designs include: Helichrome Globin-1 Cy-AA-EK Peptides IIa/IId α2 Transmembrane helical designs Later design ... June 1999). "Design and synthesis of a globin fold". Biochemistry. 38 (23): 7431-7443. doi:10.1021/bi983006y. PMID 10360940. ...
Hemoglobin synthesis comprises globin and heme synthesis. The heme molecule is formed by the attachment of an Fe2+ ion to ...
... 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. ...
1999)‎. Haplotypes of the beta-globin gene as prognostic factors in sickle-cell disease. EMHJ - Eastern Mediterranean Health ... Haplotypes of the beta-globin gene as prognostic factors in sickle-cell disease. ... Our results suggest that beta-globin gene haplotypes influence the clinical presentation of sickle-cell disease, and that there ...
The HBBP1 gene also has the most regulatory associations with active and open chromatin within the entire β-globin cluster and ... One of the iconic (yet enigmatic) arguments for human-ape common ancestry has been the β-globin pseudogene (HBBP1). ... research confirms that the HBBP1 region of the 6-gene β-globulin cluster is highly non-variable compared to the other β-globin ... genomics data showing that the HBBP1 gene is transcriptionally active and a key interactive component of the β-globin gene ...
1DXV: High-resolution X-ray Study Of Deoxy Recombinant Human Hemoglobins Synthesized From Beta-globins Having Mutated Amino ...
More info for Fold a.1: Globin-like. Timeline for Fold a.1: Globin-like: *Fold a.1: Globin-like appears in SCOP 1.57. *Fold a.1 ... Lineage for Fold a.1: Globin-like. *Root: SCOP 1.55 *. Class a: All alpha proteins [46456] (138 folds). ...
Alpha globin variation in the long-tailed macaque suggests malaria selection. View ORCID ProfileC.L. Faust, F. Rangkuti, S. G. ... Alpha globin variation in the long-tailed macaque suggests malaria selection Message Subject (Your Name) has forwarded a page ... Almost all M. fascicularis haemoglobin variation is in the alpha globin chain, encoded by two linked genes: HBA1 and HBA2. We ... We identify a range of missense mutations in M. fascicularis alpha globin and demonstrate that some of these exhibit a striking ...
1999)‎. Haplotypes of the beta-globin gene as prognostic factors in sickle-cell disease. EMHJ - Eastern Mediterranean Health ... Haplotypes of the beta-globin gene as prognostic factors in sickle-cell disease. ... Our results suggest that beta-globin gene haplotypes influence the clinical presentation of sickle-cell disease, and that there ...
The studies also suggest that lack of strong heme-globin binding does not hinder the synthesis of globin chains. ... Synthesis of hemoglobin Gun Hill: increased synthesis of the heme-free βGH globin chain and subunit exchange with a free α- ... No evidence was obtained for the existence of "slow points" in the process of globin chain assembly. ...
Alpha-globin transcription factor CP2, SAA3 enhancer factor, Transcription factor LSF, TFCP2, LSF, SEF ...
... part of the β-globin gene and about 4.5 kb of its upstream flanking region was cloned and sequenced. The sequence was compared ... Evolution of the primate beta-globin gene region: nucleotide sequence of the delta-beta-globin intergenic region of gorilla and ... Evolution of the primate beta-globin gene region: nucleotide sequence of the delta-beta-globin intergenic region of gorilla and ... Abstract : A 6.0-kb DNA fragment from Gorilla gorilla including the 5′ part of the β-globin gene and about 4.5 kb of its ...
Results show that most helices in globins can be identified by high curvature, with the exception of the C and D helices. ... Analysis of the superposition reveals that globins are most strongly conserved structurally in the mid-regions of the E and G ... The algorithm is applied to analyze a set of seven globin structures. Our method identifies 100 corresponding landmarks across ... Modeling and superposition of multiple protein structures using affine transformations: analysis of the globins. Journal ...
It has been demonstrated that increased embryonic globin (ε-globin) gene expression, similar to fetal globin (γ-globin), can ... We also found that SUV4-20h1 repressed embryonic globin gene expression in mice, suggesting a conserved role for SUV4-20h1 ... Herein, we show that a histone lysine methyltransferase, SUV4-20h1, plays a critical role in silencing ε-globin gene expression ... We found that ε-globin gene expression could be modulated by coordinate SUV4-20h1-dependent histone modification and DNA ...
Genes, Dominant, *Genes, Structural, 0 (Plasmids), 9004-22-2 (Globins), Animals, Base Sequence, Cell Line, Deoxyribonuclease I, ... Detailed analysis of the site 3 region of the human β-globin Dominant Control Region.. Publication. Publication. EMBO Journal ... Talbot, D, Philipsen, J.N.J, Fraser, P.J, & Grosveld, F.G. (1990). Detailed analysis of the site 3 region of the human β-globin ... We have delineated the hypersensitive site located 10.5 kbp upstream of the epsilon-globin gene by short range DNase I ...
3468 Single-Cell RNA Sequencing of Sickle Cell Reticulocytes to Identify Beta-Globin Genotypes and Associated Gene Expression ... is a genetic condition typically caused by a single point mutation in both copies of the beta-globin (HBB) gene, resulting in ...
The platypus α-globin cluster (chromosome 21) contains embryonic and adult α- globin genes, a β-like ω-globin gene, and the GBY ... Thus, the mammalian α- and β-globin clusters are orthologous to the bird α- and β-globin clusters respectively. We propose that ... From tandem duplication of a single globin locus, the α- and β-globin clusters expanded, and then were separated onto different ... The platypus β-globin cluster (chromosome 2) contains single embryonic and adult globin genes arranged as 5-ε-β-3. ...
Potentially Therapeutic Levels of Anti-Sickling Globin Gene Expression Following Lentivirus-mediated Gene Transfer in Sickle ... Potentially Therapeutic Levels of Anti-Sickling Globin Gene Expression Following Lentivirus-mediated Gene Transfer in Sickle ...
A Globin Domain in a Neuronal Transmembrane Receptor of Caenorhabditis Elegans and Ascaris Suum: Molecular Modeling and ...
... kb fragment that contained only the hemoglobin alpha globin gene-2 gene. This finding led to screening and follow up in first- ... in intron 1 of the hemoglobin beta globin gene and a non-pathogenic sequence variant (single nucleotide polimorfism (SNP) ... From: Combination of a triple alpha-globin gene with beta-thalassemia in a gypsy family: importance of the genetic testing in ...
COMPARATIVE EVALUATIONS, GLOBINS, HYDROGEN PEROXIDE, REDOX REACTIONS, SPECTROSCOPY, STRUCTURAL CHEMICAL ANALYSIS, ULTRAVIOLET ...
Expression of GATA-1 in a Non-hematopoietic Cell Line Induces β-Globin Locus Control Region Chromatin Structure Remodeling and ... Expression of GATA-1 in a Non-hematopoietic Cell Line Induces β-Globin Locus Control Region Chromatin Structure Remodeling and ...
Several of these microsatellites have been described within the β-globin locus and some could be involved in controlling gene ... Genetic variations in human fetal globin gene microsatellites and their functional relevance. In: Human Genetics. 1999 ; Vol. ... Several of these microsatellites have been described within the β-globin locus and some could be involved in controlling gene ... Several of these microsatellites have been described within the β-globin locus and some could be involved in controlling gene ...
annotate test-data/globins-masked.sto @ 7:b28e8ed99424 draft default tip Find changesets by keywords (author, files, the commit ...
alpha globin (HBA) gene duplications, next generation sequencing, non-transfusion dependent thalassaemia, Alleles, Gene ... Beta thalassaemia intermedia due to co-inheritance of three unique alpha globin cluster duplications characterised by next ... Beta thalassaemia intermedia due to co-inheritance of three unique alpha globin cluster duplications characterised by next ...
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. ... "beta-Globins" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... This graph shows the total number of publications written about "beta-Globins" by people in this website by year, and whether " ...
Professor of Biostatistics and Informatics
As Globin Solutions and the University of Pittsburgh have continued their discovery-based research collaboration, we have ... In this grant program, in conjunction with the University of Pittsburgh, Globin Solutions will continue to develop the ...
A single therapeutic base edit of the BCL11A enhancer prevented sickling and ameliorated globin chain imbalance in erythroid ... CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells. Nature 539, 384-389 (2016). ... Three new β-globin gene promoter mutations identified through newborn screening. Hemoglobin 31, 129-134 (2007). ... A single therapeutic base edit of the BCL11A enhancer prevented sickling and ameliorated globin chain imbalance in erythroid ...
LBDRLP - Roche LA low positive globin control. Variable Name: LBDRLP. SAS Label: Roche LA low positive globin control. English ... LBDRHP - Roche LA high positive globin control. Variable Name: LBDRHP. SAS Label: Roche LA high positive globin control. ... If beta-globin is not present, both LBDRHP and LBDRLP are negative in the sample and no HPV type is detected, the sample is ... Roche LA high positive globin control. Target: Females only 14 YEARS - 17 YEARS. Code or Value. Value Description. Count. ...
title = "Stat3β inhibits γ-globin gene expression in erythroid cells",. abstract = "We demonstrated previously γ-globin gene ... Foley, HA, Ofori-Acquah, SF, Yoshimura, A, Critz, S, Surendra Baliga, B & Pace, BS 2002, Stat3β inhibits γ-globin gene ... Stat3β inhibits γ-globin gene expression in erythroid cells. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 18. pp. ... Stat3β inhibits γ-globin gene expression in erythroid cells. Heather A. Foley, Solomon F. Ofori-Acquah, Akihiko Yoshimura, ...
  • 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. (icr.org)
  • We identify a range of missense mutations in M. fascicularis alpha globin and demonstrate that some of these exhibit a striking HBA1 or HBA2 specificity, a pattern consistent with computational simulations of selection on genes exhibiting copy number variation. (biorxiv.org)
  • We propose that M. fascicularis accumulated amino acid substitutions in its alpha globin genes under malaria selection, in a process that closely mirrors, but does not entirely converge with, human malaria adaptation. (biorxiv.org)
  • Four DNase I hypersensitive sites characterize the human beta-globin Dominant Control Region (DCR) providing position independent, high levels of erythroid specific expression to linked homologous and heterologous genes when introduced into cultured cells or in transgenic mice. (eur.nl)
  • This assay can be used instead of southern blot analysis to determine the total number of intact alpha globin genes. (fantesti.co)
  • The human genome has two linked alpha-globin genes on chromosome 16. (ox.ac.uk)
  • Deletion of one or more of them, as occurs in alpha-thalassaemia, leads to a reduced output of alpha-globin mRNA in proportion to the number of alpha-globin genes lost. (ox.ac.uk)
  • In some racial groups deletion of one of the pair of alpha-globin genes may result from unequal crossing over between the genes on homologous chromosomes by a mechanism resembling that postulated for the formation of the delta beta fusion genes of the Lepore haemoglobins. (ox.ac.uk)
  • By analogy, the opposite chromosome in this cross-over should have three alpha-globin genes just as the 'anti-Lepore chromosome has three non-alpha chain genes. (ox.ac.uk)
  • The number of globin genes in human cells was determined by hybridizing DNA from human spleens to 3 H labeled DNA complementary to human globin mRNA. (mssm.edu)
  • The α-like and β-like globin genes have provided a paradigm for the study of molecular evolution and regulation of multigene families in eukaryotes. (elsevier.com)
  • Both α-globin genes were screened for deletional and nondeletional mutations using a stepwise diagnostic strategy as described before. (elsevier.com)
  • globin genes increases the concentration of fetal hemoglobin and hemoglobin A2 in a Saudi Arabian population. (cdc.gov)
  • A sibling who is fully matched for human leukocyte antigen (HLA) and who is, at most, a carrier for alpha thalassemia (deletion of 2 alpha-globin genes) is the most suitable donor. (medscape.com)
  • and (iii) molecular analysis of the haemoglobin S mutation , the haplotype in the ß- globin -like genes cluster, the 3.7 kb α-thalassaemia gene deletion and 19 selected single- nucleotide polymorphisms ( SNPs ) associated with fetal haemoglobin (HbF) levels.Results. (bvsalud.org)
  • Mutation of β-globin gene causing translation-premature termination results in significant decrease of the mRNA abundance. (who.int)
  • In this study, α/β-globin mRNA ratio was determined by semi-quantitative RT-PCR in β-thalassemia carriers with the β17, β41/42, β71/72 and β27 mutations and in a patient with compound heterozygous β17, β27 mutations. (who.int)
  • The α/β-globin mRNA ratio of normal individual was found to be 0.98 whereas those of heterozygous for β17, β41/42, β71/72 and compound heterozygous β17/β27 were 0.89 1.66 1.60 and 3.09, respectively. (who.int)
  • This result was in concordance with the α/β-globin mRNA ratio observed. (who.int)
  • This data indicates that the α/β-globin mRNA ratio is dependent on the type and the location of premature termination mutation and related to some other factors involving NMD mechanism in cells. (who.int)
  • Enforced expression with the pTarget-HDAC9 vector produced a dose -dependent 2.5-fold increase in γ- globin mRNA (p (bvsalud.org)
  • Moreover, enforced HDAC9 expression increased γ- globin mRNA levels by 2.5-fold with a simultaneous 7-fold increase in HbF. (bvsalud.org)
  • Which globin mRNAs and rRNAs are depleted with the NEBNext® Globin mRNA & rRNA Depletion Kit (Human/Mouse/Rat)? (neb.sg)
  • 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)
  • Sickle cell disease (SCD) is a genetic condition typically caused by a single point mutation in both copies of the beta-globin (HBB) gene, resulting in sickle (S) hemoglobin (HbS) production instead of adult (A) hemoglobin (HbA). (confex.com)
  • Adult HEMOGLOBIN is comprised of two ALPHA-GLOBIN chains and two beta-globin chains. (rush.edu)
  • As Globin Solutions and the University of Pittsburgh have continued their discovery-based research collaboration, we have created modified hemoglobin molecules, originally isolated from expired human donor packed red blood cells, that have demonstrated high affinity for carbon monoxide (GSI-1901 and GSI-2001). (globinsolutions.com)
  • Predominant vertebrate peptides in all if questing ticks were examined not only for infection but pools were - and -globin chains of hemoglobin and im- also for the source of the last blood meal because the tick munoglobulins. (cdc.gov)
  • Strategies to induce fetal hemoglobin (HbF) synthesis for the treatment of ß- hemoglobinopathies probably involve protein modifications by histone deacetylases (HDACs) that mediate γ- globin gene regulation . (bvsalud.org)
  • This is accomplished by using hemoglobin (Hb), a tetramer protein composed of heme and globin. (medscape.com)
  • 8. Miller YI, Altamentova SM, Shaklai N. Oxidation of low-density lipoprotein by hemoglobin stems from a heme-initiated globin radical. (bvsalud.org)
  • MatthiasThursday, 13 September 2012 08:53:55 UTCWe have removed in our watch some moral UI melanoma for some protocol hemoglobin globins, and the Express multi-media suggests not more than preceding for our different security. (robertfischer.name)
  • After infusion, transduced CD34+ HSCs engraft in bone marrow and differentiate to produce RBCs containing biologically active beta A-T87Q -globin (a modified beta-globin protein) that combines with alpha globin to produce functional hemoglobin containing beta A-T87Q -globin (Hb A-T87Q ). (medscape.com)
  • This gene provides instructions for making a protein called beta-globin. (medlineplus.gov)
  • Modeling and superposition of multiple protein structures using affine transformations: analysis of the globins. (duke.edu)
  • DNA-protein binding studies established Stat3 interaction in the 5′-untranslated γ-globin promoter region. (elsevier.com)
  • Since the purified protein exhibited sequence homology to beta globin, globin was also isolated from rat blood by acid-acetone precipitation and was purified on Superdex-75 column in FPLC. (ias.ac.in)
  • Results obtained suggest that globin or globin-related protein present in the PMNs supernatant inhibits platelet aggregation response. (ias.ac.in)
  • Each haemoglobin molecule consists of four iron-containing parts ( haems ) and four protein chains ( globins ). (encyclopedia.com)
  • They include epsilon-globin, gamma-globin, delta-globin and beta-globin. (rush.edu)
  • Delta globin gene variations leading to reduction in HbA levels. (cdc.gov)
  • Histone deacetylase 9 activates gamma-globin gene expression in primary erythroid cells. (bvsalud.org)
  • We have delineated the hypersensitive site located 10.5 kbp upstream of the epsilon-globin gene by short range DNase I sensitivity mapping to a 600 bp region. (eur.nl)
  • It has been demonstrated that increased embryonic globin (ε-globin) gene expression, similar to fetal globin (γ-globin), can ameliorate the severity of SCD and β-thalassemia in mice. (cipsm.de)
  • We also found that SUV4-20h1 repressed embryonic globin gene expression in mice, suggesting a conserved role for SUV4-20h1 during mammalian evolution. (cipsm.de)
  • Herein, we show that a histone lysine methyltransferase, SUV4-20h1, plays a critical role in silencing ε-globin gene expression in both K562 cells and primary erythroid progenitor cells. (cipsm.de)
  • Research efforts to establish therapeutic modalities for treating sickle cell disease (SCD) and β-thalassemia have been hindered by our incomplete understanding of the developmental regulation of human β-like globin gene expression. (cipsm.de)
  • Potentially Therapeutic Levels of Anti-Sickling Globin Gene Expression Following Lentivirus-mediated Gene Transfer in Sickle Cell Disease Bone Marrow CD34(+)Cells. (stembook.org)
  • A single therapeutic base edit of the BCL11A enhancer prevented sickling and ameliorated globin chain imbalance in erythroid progeny from sickle cell disease and β-thalassemia patient-derived HSPCs, respectively. (nature.com)
  • Sickle cell disease (SCD) is caused by a point mutation in the β-globin gene and can be cured by the replacement of hematopoietic stem cells (HSCs). (cell.com)
  • Total proteins were precipitated in 95% ethanol at components, including - and -globin chains, histones, and -20°C and recovered by centrifugation. (cdc.gov)
  • Cole, LJ, Huston, WM & Moir, JWB 2008, Delivery of nitric oxide for analysis of the function of cytochrome c' . in GLOBINS AND OTHER NITRIC OXIDE-REACTIVE PROTEINS, PT A. Elsevier, SAN DIEGO, pp. 21-33. (york.ac.uk)
  • A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure. (bvsalud.org)
  • 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)
  • Origin and Expansion of Four Different Beta Globin Mutations in a Single Arab Village. (aravindachakravartilab.org)
  • Zlotogora J, Hujerat Y, Zalman L, Barges S, Filon D, Koren A, Shalev SA, Chakravarti A: Origin and Expansion of Four Different Beta Globin Mutations in a Single Arab Village. (aravindachakravartilab.org)
  • 0 0 aravinda-admin aravinda-admin 2005-05-08 20:45:05 2022-06-11 17:23:55 Origin and Expansion of Four Different Beta Globin Mutations in a Single Arab Village. (aravindachakravartilab.org)
  • First report of the spectrum of d-globin gene mutations in Omani subjects - identification of novel mutations. (cdc.gov)
  • These results identify SUV4-20h1 as a novel epigenetic suppressor of ε-globin gene expression implying a potential alternative therapeutic approach for the treatment of β-thalassemia and SCD. (cipsm.de)
  • This test can be used to detect the presence or 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. (fantesti.co)
  • DNA isolated from the spleen of a patient with β + thalassemia contained a number of globin gene copies similar to that of normal DNA. (mssm.edu)
  • thalassemia caused by novel start codon variant in conjunct with right deletion variant of ?2-globin gene]. (cdc.gov)
  • A novel deletion of the entire alpha-globin gene cluster in a British individual. (ox.ac.uk)
  • The co-inheritance of a single 3.7 kb α- globin deletion was found in 42.3% of cases (n=11). (bvsalud.org)
  • The studies also suggest that lack of strong heme-globin binding does not hinder the synthesis of globin chains. (jci.org)
  • Thalassemias are characterized by decreased production of globin (alpha and beta) chains. (medscape.com)
  • We demonstrated previously γ-globin gene inhibition in K562 cells and primary erythroid progenitors treated with interleukin-6. (elsevier.com)
  • A 6.0-kb DNA fragment from Gorilla gorilla including the 5′ part of the β-globin gene and about 4.5 kb of its upstream flanking region was cloned and sequenced. (archives-ouvertes.fr)
  • Furthermore, ChIP assays showed HDAC9 binding in vivo in the upstream Gγ- globin gene promoter region . (bvsalud.org)
  • One of the iconic (yet enigmatic) arguments for human-ape common ancestry has been the β-globin pseudogene (HBBP1). (icr.org)
  • These results cast a new light on the primate α-globin gene family, and have intriguing implications for the existence of previously unreported, functional globin-like gene(s) in the primate genomes. (elsevier.com)
  • Assuming the rates of reannealing of complementary DNA and cellular DNA are similar, the extent of hybridization of complementary DNA at various ratios of cellular DNA to complementary DNA indicate that there are fewer than 10 globin gene copies per haploid human genome. (mssm.edu)
  • Superfamilia de proteínas que contienen el pliegue de globina, que está compuesto de 6 a 8 hélices alfa dispuestas en una estructura característica que encierra el HEME. (bvsalud.org)
  • Plasmids encoding -globin cDNA (cG), Smad cDNA (cS) had been referred to previously (20,21). (biotech2012.org)
  • Haplotypes of the Alpha-Globin Gene Regulatory Element in two Brazilian Native Populations. (bvsalud.org)
  • Biochemical evidence for functionality is indicated by multiple categories of functional genomics data showing that the HBBP1 gene is transcriptionally active and a key interactive component of the β-globin gene network. (icr.org)
  • Betibeglogene autotemcel is an autologous one-time gene therapy that adds functional copies of a modified beta-globin gene into the patients' hematopoietic stem cells (HSCs) through transduction of autologous CD34+ cells with BB305 lentiviral vector (LVV). (medscape.com)
  • We report here the complete nucleotide sequence of a gene located immediately downstream from the adult α1-globin gene of the orang-utan, along with its flanking DNA. (elsevier.com)
  • The putative polypeptide is 141 amino acids long, identical to that of the α- or ζ-globin, but its predicted amino-acid sequence is nearly as different from the orang-utan α-globin (55 differences) as the human ζ-globin is from the human α-globin (59 differences), suggesting an ancient history for the θ1 -globin gene. (elsevier.com)
  • Recently, we have isolated the adult α-globin gene region from orang-utan, olive baboon and rhesus macaque by molecular cloning. (elsevier.com)
  • No evidence was found to suggest heterogeneity of genetic linkage between alpha-globin and the APKD locus in this population. (ox.ac.uk)
  • Methylene violet staining for the evaluation of HbH-IBs' reduction, in HbH RBCs upon incubation with 10xHisXa SITE -TAT-α-globin-HA. (biomedcentral.com)
  • A Untreated HbH patient's RBCs, and B HbH patient's RBCs incubated with IBs, enriched in 10xHis-Xa SITE -TAT-α-globin-HA, for 48 h. (biomedcentral.com)
  • Therefore, elucidating the molecular mechanism of ε-globin gene silencing is of biologic and clinical importance. (cipsm.de)
  • characterized by a decrease or complete absence of As a chronic disorder, thalassaemia is a clinical and globin chain production ( 1 ). (who.int)
  • Dikshit, Madhu (2002) Inhibition of platelet aggregation by rat globin Thrombosis Research: Vascular Obstruction, Hemorrhage and Hemostasis, 107 (5). (ias.ac.in)
  • 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. (icr.org)
  • RePub, Erasmus University Repository: Detailed analysis of the site 3 region of the human β-globin Dominant Control Region. (eur.nl)
  • CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells. (nature.com)
  • The primer mix amplifies essentially all HPV types found in the genital tract along with the human β-globin gene. (cdc.gov)
  • Sickle cell anemia is caused by a point mutation on the DNA of the beta-globin chain. (medscape.com)
  • An alternative analysis of the data, which introduces no assumptions concerning the relative rates of reaction of complementary DNA and cellular DNA, indicates fewer than 20 globin gene copies are present. (mssm.edu)
  • beta-Globins" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (rush.edu)
  • Methemoglobinemia, beta-globin type is a condition that affects the function of red blood cells. (medlineplus.gov)
  • The signs and symptoms of methemoglobinemia, beta-globin type are generally limited to cyanosis, which does not cause any health problems. (medlineplus.gov)
  • The incidence of methemoglobinemia, beta-globin type is unknown. (medlineplus.gov)
  • We therefore conclude that a combination of factor binding sites is necessary to allow site 3 to function as a strong transcriptional activator, resulting in position independent expression of the beta-globin gene. (eur.nl)
  • Beta thalassaemia intermedia due to co-inheritance of three unique alpha globin cluster duplications characterised by next generation sequencing analysis. (ox.ac.uk)
  • Members of the beta-globin family. (rush.edu)
  • This graph shows the total number of publications written about "beta-Globins" by people in this website by year, and whether "beta-Globins" was a major or minor topic of these publications. (rush.edu)
  • Below are the most recent publications written about "beta-Globins" by people in Profiles. (rush.edu)
  • Globin-gene mapping of DNA from 13 families with normal Hb A2 beta-thalassaemia (both type 1 and type 2) failed to detect any difference from normal in their globin-gene arrangement. (ox.ac.uk)
  • Seven polymorphic sites in the beta-globin gene cluster were analyzed on a sample of 96 chromosomes of Venezuelan sickle cell patients from the State of Aragua. (embrapa.br)
  • The factor involved behind the sickling of RBC is the mutant of Beta Globin cistron located in chromosome 11. (freebooksummary.com)
  • About one 3rd autochthonal people of Sub- Saharan Africa bear this mutated Beta globin cistron. (freebooksummary.com)
  • globin cistron of chromosome 11, which consequences in the permutation of hydrophilic glutamic acidA to hydrophobic A valineA at the 6th place gives rise to mutated beta hematohiston sub unit. (freebooksummary.com)
  • No evidence was obtained for the existence of "slow points" in the process of globin chain assembly. (jci.org)
  • We demonstrate that alpha globin variation in M. fascicularis correlates with the strength of malaria selection. (biorxiv.org)
  • Results show that most helices in globins can be identified by high curvature, with the exception of the C and D helices. (duke.edu)
  • Analysis of the superposition reveals that globins are most strongly conserved structurally in the mid-regions of the E and G helices. (duke.edu)
  • we observed 40 and 60% γ- globin gene silencing in day 11 (early) and day 28 (late) progenitors. (bvsalud.org)
  • Samples that were negative for HPV and the β-globin control indicated lack of a suitable sample and were considered inadequate for interpretation (Linear Array HPV Genotyping Test Application manual, 2008). (cdc.gov)