TY - JOUR. T1 - Stimulation of human and rat islet β-cell proliferation with retention of function by the homeodomain transcription factor Nkx6.1. AU - Schisler, Jonathan C.. AU - Fueger, Patrick T.. AU - Babu, Daniella A.. AU - Hohmeier, Hans E.. AU - Tessem, Jeffery S.. AU - Lu, Danhong. AU - Becker, Thomas C.. AU - Naziruddin, Bashoo. AU - Levy, Marlon. AU - Mirmira, Raghavendra G.. AU - Newgard, Christopher B.. PY - 2008/5/1. Y1 - 2008/5/1. N2 - The homeodomain transcription factor Nkx6.1 plays an important role in pancreatic islet β-cell development, but its effects on adult β-cell function, survival, and proliferation are not well understood. In the present study, we demonstrated that treatment of primary rat pancreatic islets with a cytomegalovirus promoter-driven recombinant adenovirus containing the Nkx6.1 cDNA (AdCMV-Nkx6.1) causes dramatic increases in [methyl-3H] thymidine and 5-bromo-2′-deoxyuridine (BrdU) incorporation and in the number of cells per islet relative to islets ...
Barretts esophagus (BE) is an intestinal metaplasia that occurs in the setting of chronic acid and bile reflux and is associated with a risk for adenocarcinoma. Expression of intestine-specific transcription factors in the esophagus likely contributes to metaplasia development. Our objective was to explore the effects of an intestine-specific transcription factor when expressed in the mouse esophageal epithelium. Transgenic mice were derived in which the transcription factor Cdx2 is expressed in squamous epithelium using the murine Keratin-14 gene promoter. Effects of the transgene upon cell proliferation and differentiation, gene expression, and barrier integrity were explored. K14-Cdx2 mice express the Cdx2 transgene in esophageal squamous tissues. Cdx2 expression was associated with reduced basal epithelial cell proliferation and altered cell morphology. Ultrastructurally two changes were noted. Cdx2 expression was associated with dilated space between the basal cells and diminished ...
Invasion and metastasis are the hallmarks of malignant tumor progression and the main cause of death in cancer. The embryonic program epithelial-mesenchymal transition (EMT) is thought to trigger invasion by allowing tumor cell dissemination. Here, we describe that the EMT-inducing transcriptional repressor ZEB1 promotes colorectal cancer cell metastasis and loss of cell polarity. Thereby, ZEB1 suppresses the expression of cell polarity factors, in particular of Lgl2, which we found reduced in colorectal and breast cancers. We further show that retention of Lgl2 expression is critical for the epithelial phenotype and that its loss might be involved in metastasis. Thus, by linking EMT, loss of polarity, and metastasis, ZEB1 is a crucial promoter of malignant tumor progression. [Cancer Res 2008;68(2):537-44]. ...
The Dlx homeobox gene family is expressed in a complex pattern within the embryonic craniofacial ectoderm and ectomesenchyme. A previous study established that Dlx-2 is essential for development of proximal regions of the murine first and second branchial arches. Here we describe the craniofacial ph …
Homeodomain transcription factors control developmental processes. They pattern body formation, specify cell lineages and switch the onset of gene regulatory cascades. Pitx2, a bicoid-related homeodomain transcription factor, is asymmetrically expressed in the left lateral plate mesoderm and mesoderm-derived tissues. Pitx2 null mice are characterized by failure of body wall closure, axial and cardiac malformations and arrest of organ development. By analyzing Pitx2 expression pattern and phenotype of Pitx2 null mice, we have established that (1) Pitx2 is a universal muscle marker, because it marks the muscle lineage more completely that any of the known markers, (2) expression of Pitx2 precedes the onset of myogenic progression in the cephalic mesoderm and mesodermal core of first BA and activates the transcription factors Tbx1, Tcf21, and Msc, (3) Pitx2 follows the onset of myogenic progression in the somitic mesoderm, (4) loss of Pitx2 leads to absence of extraocular, mastication and abdominal ...
High-risk breast cancer comprises distinct tumor entities such as triple-negative breast cancer (TNBC) which is characterized by lack of estrogen (ER) and progesterone (PR) and the |i|HER2|/i| receptor and breast malignancies which have spread to more than three lymph nodes. For such patients, current (inter)national guidelines recommend anthracycline-based chemotherapy as the standard of care, but not all patients do equally benefit from such a chemotherapy. To further improve therapy decision-making, predictive biomarkers are of high, so far unmet, medical need. In this respect, predictive biomarkers would permit patient selection for a particular kind of chemotherapy and, by this, guide physicians to optimize the treatment plan for each patient individually. Besides DNA mutations, DNA methylation as a patient selection marker has received increasing clinical attention. For instance, significant evidence has accumulated that methylation of the |i|PITX2|/i| (paired-like homeodomain transcription factor
This gene encodes a paired-like homeodomain transcription factor in the developing pituitary gland. Expression occurs prior to and is required for expression of pou domai
Looking for Homeodomain protein? Find out information about Homeodomain protein. A highly conserved sequence of deoxyribonucleic acid that occurs in the coding region of development-controlling regulatory genes and codes for a protein... Explanation of Homeodomain protein
Hox proteins are transcriptional regulators that specify cell fate during early embryonic development and organogenesis (reviewed by Krumlauf, 1994). However, Hox protein monomers display poor specificity and affinity for enhancer sequences, suggesting that they do not act in isolation. Recently, two families of Hox cofactors, Pbx and Meis, belonging to the TALE (Three Amino acid Loop Extension) homeodomain superfamily, were identified (reviewed by Mann and Affolter, 1998). In vitro analyses indicate that Meis and Pbx function by forming multimeric complexes with Hox proteins. In particular, Pbx binds to Hox proteins from paralog group 1-10 (Shen et al., 1997b) and Meis binds to Hox proteins from paralog group 9-13 (Shen et al., 1997a). Meis and Pbx also interact, via the Meinox domain (particularly the M1 and M2 subdomains) in Meis and the PBC-A and PBC-B domains in Pbx (reviewed by Mann and Affolter, 1998), to permit the formation of Meis/Pbx/Hox trimers (Berthelsen et al., 1998a; Jacobs et ...
Pbx genes encode TALE class homeodomain transcription factors that pattern the developing neural tube, pancreas, and blood. Within the hindbrain, Pbx cooperates with Hox proteins to regulate rhombomere segment identity. Pbx cooperates with Eng to regulate midbrain-hindbrain boundary maintenance, and with MyoD to control fast muscle cell differentiation. Although previous results have demonstrated that Pbx is required for proper eye size, functions in regulating retinal cell identity and patterning have not yet been examined. Analysis of retinal ganglion cell axon pathfinding and outgrowth in pbx2/4 null embryos demonstrated a key role for pbx genes in regulating neural cell behavior. To identify Pbx-dependent genes involved in regulating retino-tectal pathfinding, we conducted a microarray screen for Pbx-dependent transcripts in zebrafish, and detected genes that are specifically expressed in the eye and tectum. A subset of Pbx-dependent retinal transcripts delineate specific domains in the dorso
Homeotic genes are key developmental regulators that are highly conserved throughout evolution. Their encoded homeoproteins function as transcription factors to control a wide range of developmental processes. Although much is known about homeodomain-DNA interactions, only a small number of genes acting downstream of homeoproteins have been identified. Here we use a functional genomic approach to identify candidate target genes of the Drosophila homeodomain transcription factor Labial. High-density oligonucleotide arrays with probe sets representing 1,513 identified and sequenced genes were used to analyze differential gene expression following labial overexpression in Drosophila embryos. We find significant expression level changes for 96 genes belonging to all functional classes represented on the array. In accordance with our experimental procedure, we expect that these genes are either direct or indirect targets of labial gene action. Among these genes, 48 were upregulated and 48 were downregulated
Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).
TY - JOUR. T1 - Efficient generation of hepatoblasts from human ES cells and iPS cells by transient overexpression of homeobox gene HEX. AU - Inamura, Mitsuru. AU - Kawabata, Kenji. AU - Takayama, Kazuo. AU - Tashiro, Katsuhisa. AU - Sakurai, Fuminori. AU - Katayama, Kazufumi. AU - Toyoda, Masashi. AU - Akutsu, Hidenori. AU - Miyagawa, Yoshitaka. AU - Okita, Hajime. AU - Kiyokawa, Nobutaka. AU - Umezawa, Akihiro. AU - Hayakawa, Takao. AU - Furue, Miho K.. AU - Mizuguchi, Hiroyuki. N1 - Funding Information: We thank Hiroko Matsumura and Midori Hayashida for their excellent technical support. This study was supported by grants from the Ministry of Education, Sports, Science and Technology of Japan (20200076) and by grants from the Ministry of Health, Labor, and Welfare of Japan.. PY - 2011/2. Y1 - 2011/2. N2 - Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the potential to differentiate into all cell lineages, including hepatocytes, in vitro. Induced hepatocytes ...
Hox transcription factors are extensively investigated in diverse fields of molecular and evolutionary biology. Hox genes belong to the family of homeobox transcription factors characterised by a 60 amino acids region called homeodomain. These genes are evolutionary conserved and play crucial roles in the development of animals. In particular, they are involved in the specification of segmental identity, and in the tetrapod limb differentiation. In vertebrates, this family of genes can be divided into 14 groups of homology. Common methods to classify Hox proteins focus on the homeodomain. Classification is however hampered by the high conservation of this short domain. Since phylogenetic tree reconstruction is time-consuming, it is not suitable to classify the growing number of Hox sequences. The first goal of this thesis is therefore to design an automated approach to classify vertebrate Hox proteins in their groups of homology. This approach classifies Hox proteins on the basis of their scores ...
Pathogenic variations of the ARX (aristaless-related homeobox) gene are associated with marked phenotypic pleiotropy. These phenotypes are X-linked neurological disorders that include brain and genital malformation and non-malformation syndromes. Typically, malformation phenotypes result from pathogenic variations that are predicted to truncate the ARX protein, or alter residues in the highly conserved homeodomain. While non-malformation phenotypes tend to be caused by pathogenic variations that are predicted to expand the first two polyalanine tracts of ARX, or alter residues outside of the homeodomain. The most common pathogenic variation of the ARX gene is a duplication of 24 bp, c.429_452 dup, which leads to an expansion of the second polyalanine tract of the ARX protein from 12 to 20 alanine residues. This pathogenic variation is associated with both sporadic and familial nonsyndromic mental retardation. Syndromic manifestations include mental retardation with hand dystonia (Partington ...
Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the DPRX homeobox gene family. Evidence of mRNA expression has not yet been found for this gene. Multiple, related processed pseudogenes have been found which are thought to reflect expression of this gene in the germ line or embryonic cells. [provided by RefSeq, Jul 2008 ...
Hox genes encode evolutionarily conserved transcription factors involved in the specification of segmental identity during embryonic development. This specification of identity is thought to be directed by differential Hox gene action, based on differential spatiotemporal expression patterns, protein sequence differences, interactions with co-factors and regulation of specific downstream genes. During embryonic development of the Drosophila brain, the Hox gene labial is required for the regionalized specification of the tritocerebral neuromere; in the absence of labial, the cells in this brain region do not acquire a neuronal identity and major axonal pathfinding deficits result. We have used genetic rescue experiments to investigate the functional equivalence of the Drosophila Hox gene products in the specification of the tritocerebral neuromere. Using the Gal4-UAS system, we first demonstrate that the labial mutant brain phenotype can be rescued by targeted expression of the Labial protein ...
In human cancer cells of the colon and other epithelial tissues, the level of p27Kip1 is frequently reduced by its accelerated degradation through proteasomes (36, 37). The reduced level of p27Kip1 is also correlated with poor prognosis, suggesting its tumor-suppressing activity (25). Consistently, homozygous p27Kip1 mutation increased the number of intestinal polyps in Apc mutant mice by 5 to 6 times (38). In colon cancer cells, however, the mechanism that stimulates the degradation of p27Kip1 was unknown. Here we have shown that homeobox transcription factor CDX2 stabilizes p27Kip1 by blocking its proteolysis (Figs. 3 and 4). Interestingly, we have found a significant correlation between CDX2 and p27Kip1 protein levels in human colon cancer tissues (Fig. 6). Our present results suggest that the decreased level of CDX2 is one of the causes that stimulate the p27Kip1 proteolysis in colon cancer cells.. During the G1 to S transition, phosphorylation of p27Kip1 at T187 triggers its proteasomal ...
First, the model proposes EXD as a required co‐activator for most HOX target elements. All known elements activated in response to HOX proteins also require exd function (Chan et al., 1994, 1996; Rauskolb and Wieschaus, 1994; Popperl et al., 1995; Sun et al., 1995). Based on the phenotypes of exdmz− mutants and of clones of exd mutant cells in adult cuticular structures (Peifer and Wieschaus, 1990; Gonzalez‐Crespo and Morata, 1995; Rauskolb et al., 1995), it seems likely that a great many other HOX target elements also require exd for their activation. The only HOX protein that appears to have some exd‐independent activation function is ABD‐B (Peifer and Wieschaus, 1990). This correlates with the absence of a YPWM motif just upstream of the ABD‐B homeodomain sequence. The YPWM or hexapeptide motif is required for the formation of HOX-EXD or HOX-PBX cooperative binding complexes (Chang et al., 1995; Johnson et al., 1995; Knoepfler and Kamps, 1995; Neuteboom et al., 1995; Phelan et ...
Buy Anti-Nkx3.1 (Nkx-3.1, BAPX2, Homeobox protein Nkx3.1, Homeobox Protein Nkx-3.1, NK Homeobox (Drosoph, item number: N2850-30K.100 from United States Biological at Biomol!
In Drosophila, the Hox gene Ultrabithorax (Ubx) specifies the development of two different metameres--parasegment 5, which is entirely thoracic, and parasegment 6, which includes most of the first abdominal segment. Here we investigate how a single Hox gene can specify two such different morphologies. We show that, in the early embryo, cells respond similarly to UBX protein in both parasegments. The differences between parasegments 5 and 6 can be explained by the different spatial and temporal pattern of UBX protein expression in these two metameres. We find no evidence for multiple threshold responses to different levels of UBX protein. We examine in particular the role of Ubx in limb development. We show that UBX protein will repress limb primordia before 7 hours, when Ubx is expressed in the abdomen, but not later, when UBX is first expressed in the T3 limb primordium. The regulation of one downstream target of UBX, the Distalless gene, provides a model for this transition at the molecular ...
Introduction: The Dlx1/Dlx2 double knockout mouse has reduced numbers (33% fewer) of retinal ganglion cells (RGC), due to enhanced apoptosis. Brn3a and Brn3b are closely related members of the Class IV POU-domain gene family, and play functionally interchangeable roles in retinal development. We hypothesized that Brn3a and/or Brn3b are direct DLX transcriptional targets during retinal development. Methods: Chromatin immunoprecipitation (ChIP) assays were performed on E16.5 retinas to identify DLX proteins bound to the Brn3a or Brn3b promoters. Electrophoretic mobility shift assays (EMSA) were used to confirm the specificity of this binding. Luciferase reporter gene assays were performed to confirm the functional significance of DLX binding to the Brn3 or Brn3ba promoters in vitro. In utero retinal electroporation was used to study the effect of DLX gain-of-function on Brn3a/Brn3b expression in vivo. Compound Dlx1/Dlx2/Brn3a and Dlx1/Dlx2/Brn3b knockout mice were generated for analysis of retinal ...
The homeodomain transcription factor, Irx5, negatively regulates KV4.2 expression in the heart, forming an inverse transient outward K+ current (Ito,f) gradient from epicardium (EPI) to endocardium (ENDO) that ensures coordinated cardiac repolarization. Loss of Irx5 in mice (i.e. Irx5−/−) eliminated the KV4.2 and Ito,f gradients, leading to increased susceptibility to tachyarrhythmias. To further investigate the cardiac role of Irx5, we examined the contractile properties of Irx5−/− mouse heart. Compared to control, Irx5−/− hearts displayed lower cardiac contractility as measured either in in vivo or in isolated Langendorff perfused hearts. Consistent with previous studies showing that Ito,f levels regulate Ca2+ entry and contractility via modulation of action potential (AP) profile, we observed that isolated ENDO ventricular myocytes from Irx5−/− had reduced cell shortening and [Ca2+]i transients along with increased Ito,f and abbreviated AP durations compared to control. By ...
Developmental reprogramming of splenic vasculature and homeostasis of B-1a cells in Nkx2.3 homeodomain transcription factor deficient mouse ...
insulin promoter factor 1: PDX-1/IPF1/STF-1/IDX-1/IUF-1 is a homeodomain containing transcription factor; found in pancreatic beta-cells; RIPE3b1 was cloned and identified as the mammalian homologue of an avian regulator of cellular differentiation MafA/L-Maf; amino acid sequence in first source; RerSeq NM_008814 (mouse), NM_013311 (human), NM_022852
Homeodomain-containing proteins are transcription regulators controlling the coordinated expression of genes involved in development, differentiation, and cellular transformation. They share a highly conserved 60-amino-acid region (the homeodomain), which allows them to bind DNA and modulate the e …
The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are subsequently re-expressed in many types of cancer. Some recent studies have shown that HOX genes may have key roles both in pancreatic development and in adult diseases of the pancreas, including cancer. In this review we consider recent advances in elucidating the role of HOX genes in these processes, how they may connect early developmental events to subsequent adult disease, and their potential both as diagnostic markers and therapeutic targets.. ...
J:48576 Sussel L, Kalamaras J, Hartigan-OConnor DJ, Meneses JJ, Pedersen RA , Rubenstein JL , German MS, Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic beta cells. Development. 1998 Jun;125(12):2213-21 ...
TY - JOUR. T1 - A short, disordered protein region mediates interactions between the homeodomain of the yeast α2 protein and the MCM1 protein. AU - Vershon, Andrew K.. AU - Johnson, Alexander D.. PY - 1993/1/15. Y1 - 1993/1/15. N2 - Homeodomains are folded into a characteristic three-dimensional structure capable of recognizing DNA in a sequence-specific manner. We show that correct target site selection by the yeast α2 protein requires, as well as its homeodomain, an adjacent short and apparently unstructured region of the protein. This flexible homeodomain extension is responsible for specifying an interaction with a second regulatory protein, MCM1, which permits the cooperative binding of the two proteins to an operator. Two additional experiments suggest that this extension-homeodomain arrangement is likely to have some generality. First, when the extension of α2 is grafted onto the Drosophila engrailed homeodomain, it yields a protein with the DNA binding specificity of engrailed and the ...
This locus is a processed pseudogene of the transcription factor NANOG. NANOG plays a central role in regulating self-renewal in pluripotent stem cells and tumor cells. This pseudogene contains an intact open reading frame that could potentially encode a protein similar to NANOG. Although there is no evidence of transcription from this pseudogene, RT-PCR studies suggest that NANOGP8 may be expressed in some cancer cell lines. In vitro studies using a recombinant NANOGP8 protein have shown that the protein localizes to the nucleus and can promote cell proliferation, similar to NANOG. [provided by RefSeq, Sep 2009 ...
Hox complex genes are key developmental regulators highly conserved throughout evolution. They encode transcription factors that initiate genetic programs of diversified morphogenesis along the anteroposterior embryonic axis. We report the characterization of the novel Drosophila Hox target gene dlarp, isolated from a further screen of a previously described library of genomic DNA fragments associated in vivo with Ultrabithorax proteins. The dlarp spatio-temporal pattern of transcription in wild-type and homeotic mutant embryos is consistent with a positive regulation by Sex combs reduced and Ultrabithorax in the parasegment 2 ectoderm and the abdominal mesoderm, respectively. The teashirt gene product, thought to act in concert with Hox proteins, is also required for the transcriptional control of this target. Search in databases revealed that dlarp has been highly conserved during evolution. The embryonic expression pattern of the mouse orthologue does not support a function downstream of Hox ...
Vertebrate Hox and Otx genes encode homeodomain-containing transcription factors thought to transduce positional information along the body axis in the segmental portion of the trunk and in the rostral brain, respectively. Moreover, Hox and Otx2 genes show a complementary spatial regulation during embryogenesis. A 1821-base pair (bp) upstream DNA fragment of the Otx2 gene is positively regulated by co-transfection with expression vectors for the human HOXB1, HOXB2, and HOXB3 proteins in an embryonal carcinoma cell line (NT2/D1) and a shorter fragment of only 534 bp is able to drive this regulation. The HOXB1, HOXB2, and HOXB3 DNA-binding region on the 534-bp Otx2 genomic fragment has been demonstrated using nuclear extracts from Hox-transfected COS cells and 12.5 days postcoitum mouse embryos or HOXB3 homeodomain-containing bacterial extracts. HOXB1, HOXB3, and nuclear extracts from 12.5 day mouse embryos bind to a sequence containing two palindromic TAATTA sites, which bear four copies of the ...
This is the first systemic report on the expression of 39 HOX genes in both noncancerous esophageal mucosa and in ESCC. In noncancerous mucosa, we found that 5 of 39 HOX genes (HOXA2, HOXA7, HOXA9, HOXC6, and HOXC9) were expressed, and others were not detectable in our study. Three of these five expressed HOX genes (HOXA7, HOXA9, and HOXC6) were also expressed in ESCC, and the expression level is significantly lower in noncancerous mucosa than in cancer tissue. It is widely accepted that HOX genes play a crucial role as molecular address labels in early embryogenesis by conferring cell fate and establishing regional identity in tissues. However, HOX gene expression is not restricted to early development but also observed in differentiated cells of adult tissues. To better understand the functionality of HOX gene expression in adult tissues in physiologic and pathologic phenomena, and the potential role in pathogenesis, it is important to determine the expression profiles of HOX genes in specific ...
Acts as a transcriptional activator by binding to an A/T-rich sequence, the FLAT element, in the insulin gene promoter. Required for development of the roof plate and, in turn, for specification of dorsal cell fates in the CNS and developing vertebrae (By similarity).
1HDD: Crystal structure of an engrailed homeodomain-DNA complex at 2.8 A resolution: a framework for understanding homeodomain-DNA interactions.
Organogenesis is dependent on the formation of distinct cell types within the embryo. Important to this process are the hox genes, which are believed to confer positional identities to cells along the anteroposterior axis. Here, we have identified the caudal-related gene cdx4 as the locus mutated in kugelig (kgg), a zebrafish mutant with an early defect in haematopoiesis that is associated with abnormal anteroposterior patterning and aberrant hox gene expression. The blood deficiency in kgg embryos can be rescued by overexpressing hoxb7a or hoxa9a but not hoxb8a, indicating that the haematopoietic defect results from perturbations in specific hox genes. Furthermore, the haematopoietic defect in kgg mutants is not rescued by scl overexpression, suggesting that cdx4 and hox genes act to make the posterior mesoderm competent for blood development. Overexpression of cdx4 during zebrafish development or in mouse embryonic stem cells induces blood formation and alters hox gene expression. Taken ...
The homeodomain transcription factor Pdx1 is required for pancreas development, including the differentiation and function of β cells. Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic β cell growth and function. To investigate whether β cell failure in Irs2-/- mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2-/- mice. Before the onset of diabetes, Pdx1 was reduced in islets from Irs2-/- mice, whereas it was expressed normally in islets from wild-type or Irs1-/- mice, which do not develop diabetes. Whereas male Irs2-/-Pdx1+/+ mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2-/- mice. By contrast, transgenic expression of Pdx1 restored ...
The homeodomain transcription factor Pdx1 is required for pancreas development, including the differentiation and function of β cells. Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic β cell growth and function. To investigate whether β cell failure in Irs2-/- mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2-/- mice. Before the onset of diabetes, Pdx1 was reduced in islets from Irs2-/- mice, whereas it was expressed normally in islets from wild-type or Irs1-/- mice, which do not develop diabetes. Whereas male Irs2-/-Pdx1+/+ mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2-/- mice. By contrast, transgenic expression of Pdx1 restored ...
The specificity of action of Hox gene products in vivo is probably achieved through the activity of still ill‐defined co‐factors modulating their transcriptional functions. Requirement for such factors in vivo would account for the relatively relaxed target specificity displayed by Hox proteins in vitro. While Hox gene products are apparently able to regulate transcription in a co‐factor‐independent manner (Zappavigna et al., 1991; Arcioni et al., 1992; Jones et al., 1992, 1993; Pöpperl and Featherstone, 1992), regulation of some target genes in vivo was indeed shown to require the presence of additional factors (Chan et al., 1994; Pöpperl et al., 1995; Gross and McGinnis, 1996). The products of the exd/Pbx genes have been proposed as Hox co‐factors on the basis of genetic analysis and of their ability to modulate DNA binding of Hox proteins in vitro (reviewed in Mann and Chan, 1996). A large amount of data has been gathered on site‐selective and cooperative DNA binding by Pbx and ...
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Meis1 and Prep1 homeodomain-containing transcription factors are essential for the normal embryonic development of several tissues and organs. Although they both can recruit Pbx at least for some of their biological function using the same homology region, the Meis1-Pbx and Prep1-Pbx complexes bind different DNA sequences and play opposite roles in tumorigenicity. In cancer, Meis1 has been extensively implicated in leukemia and neuroblastoma. Overexpression of Meis1 greatly shortens the latency and affects the penetrance of myeloid leukemia induced by Hox genes retroviral transduction. Furthermore, Meis1 has essential oncogenic function in all human leukemic MLL- translocation. Although, Meis1 is strongly suggested for involvement in human neuroblastoma and glioma, its function in non-hematological malignancies and solid tumors remains poorly defined. In contrast, Prep1 does not accelerate Hox-induced leukemogenesis. In fact heterozygous or homozygous Prep1-deficient mice develop tumors at high ...
HD proteins represent a large family of developmental regulators that, when misexpressed, represent an equally large pool of potential oncoproteins. Hox HD oncoproteins, such as HoxB8, dimerize on DNA with Pbx1, whose transcriptionally activated form, E2a-Pbx1, is also an oncoprotein. Thus, both members of this transcription factor complex can cause oncogenesis, a paradigm also observed for the Fos and Jun constituents of AP1 (36). As in the case of Fos and Jun, the mechanism of leukemogenesis by certain class I Hox proteins and E2a-Pbx1 may proceed through transcriptional targeting of a common subset of genes, Hox proteins acting in concert with endogenous Pbx proteins, and E2a-Pbx1 acting in concert with endogenous Hox proteins. The implication that Meis1 and HoxA7 or HoxA9 are involved in myeloid transformation presents another instance of potential cooperativity of oncoproteins (32); however, although the simplest hypothesis is that Meis1 and HoxA7 or HoxA9 themselves heterodimerize, ...
Hox genes encode a family of transcriptional regulators that elicit distinct developmental programmes along the head-to-tail axis of animals. The specific regional functions of individual Hox genes largely reflect their restricted expression patterns, the disruption of which can lead to developmental defects and disease. Here, we examine the spectrum of molecular mechanisms controlling Hox gene expression in model vertebrates and invertebrates and find that a diverse range of mechanisms, including nuclear dynamics, RNA processing, microRNA and translational regulation, all concur to control Hox gene outputs. We propose that this complex multi-tiered regulation might contribute to the robustness of Hox expression during development.. ...
Individual PREP1 and PBX1 are homeodomain transcriptional elements, whose biochemical and structural characterization hasnt yet been defined fully. of eukaryotic DNA-binding protein that control transcription of a wide selection of developmentally essential genes [1]. These protein talk about a 60 amino acidity DNA-binding domains which includes been conserved in series, system and framework of DNA-binding. While monomeric homeodomain protein exhibit a restricted capability to discriminate between different DNA sequences, their specificity is enhanced through the cooperative binding with various other DNA binding partners significantly. PBX1 (pre-B-cell leukemia homeobox 1) [2,3], and PREP1 (PBX-regulating proteins 1) also called PKNOX1 [4] both participate in the TALE category of homeodomain protein and form a solid and steady DNA-independent complicated [5]. PBX1 includes a nuclear localization indication and holds PREP1 in to the nucleus while subsequently PREP1 stops PBX1 nuclear export ...
Complete information for MIXL1 gene (Protein Coding), Mix Paired-Like Homeobox, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for CRX gene (Protein Coding), Cone-Rod Homeobox, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
A controversy seems to be brewing over some recent theories and quantitative analyses addressing the fundamental question of how the Bicoid morphogen gradient is established and decoded in early Drosophila embryos. The transcription factor Bicoid controls the anterior-posterior patterning of the developing embryo. It is translated from maternal mRNA localized at the anterior pole of the egg and its graded distribution activates, in a concentration-dependent manner, the expression of gap genes, thus determining their spatial domain of expression. Synthesis from a localized source combined with diffusion and uniform degradation of the Bicoid morphogen provides one of the simplest models to explain the approximately exponential shape of its gradient. BACK TO ARTICLE. ...
BC161760 - Xenopus tropicalis paired-like homeobox 2b, mRNA (cDNA clone MGC:186620 IMAGE:8956276), complete cds. EF185885 - Scyliorhinus canicula Phox2b (Phox2b) mRNA, partial cds. HQ690104 - Polyodon spathula Phox2b (Phox2b) mRNA, partial cds. AJ251458 - Gallus gallus partial mRNA for Phox2b protein (phox2b gene). Y14493 - Mus musculus mRNA for PHOX2b protein. AY371498 - Xenopus laevis homeodomain protein (phox2b) mRNA, complete cds. AY846871 - Danio rerio paired-like homeobox 2b (phox2b) mRNA, complete cds. AY883168 - Danio rerio paired-like homeobox 2b (phox2b) mRNA, complete cds. BC162881 - Danio rerio paired-like homeobox 2b, mRNA (cDNA clone MGC:194287 IMAGE:9037295), complete cds. BC162887 - Danio rerio paired-like homeobox 2b, mRNA (cDNA clone MGC:194293 IMAGE:9037291), complete cds. BC079610 - Mus musculus paired-like homeobox 2b, mRNA (cDNA clone MGC:90726 IMAGE:30360139), complete cds ...
Combinations of LIM homeodomain proteins form a transcriptional LIM code to direct the specification of neural cell types. Two paralogous pairs of LIM homeodomain proteins, LIM homeobox protein 3/4 (Lhx3/Lhx4) and Islet-1/2 (Isl1/Isl2), are expressed in developing ventral motor neurons. Lhx3 and Isl1 interact within a well characterized transcriptional complex that triggers motor neuron development, but it was not known whether Lhx4 and Isl2 could participate in equivalent complexes. We have identified an Lhx3-binding domain (LBD) in Isl2 based on sequence homology with the Isl1(LBD) and show that both Isl2(LBD) and Isl1(LBD) can bind each of Lhx3 and Lhx4. X-ray crystal- and small-angle x-ray scattering-derived solution structures of an Lhx4·Isl2 complex exhibit many similarities with that of Lhx3·Isl1; however, structural differences supported by mutagenic studies reveal differences in the mechanisms of binding. Differences in binding have implications for the mode of exchange of protein ...
TY - JOUR. T1 - The pancreatic duodenal homeobox-1 protein (Pdx-1) interacts with histone deacetylases Hdac-1 and Hdac-2 on low levels of glucose. AU - Mosley, Amber L.. AU - Özcan, Sabire. PY - 2004/12/24. Y1 - 2004/12/24. N2 - We have previously demonstrated that high concentrations of glucose stimulate insulin gene expression by causing hyperacetylation of histone H4 at the insulin gene promoter. Furthermore, we have shown that the glucose-mediated hyperacetylation of histone H4 depends on the recruitment of the histone acetyltransferase p300 by the beta cell-specific transcription factor Pdx-1. In this study, we demonstrate that the histone deacetylases Hdac-1 and Hdac-2 are rapidly recruited to the insulin promoter in the mouse insulinoma cell line MIN6 when cells are switched from high to low glucose media. Moreover, we demonstrate that the beta cell-specific homeodomain protein Pdx-1 interacts with histone deacetylases Hdac-1 and Hdac-2 at low levels of glucose. In vitro studies indicate ...
The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are dys-regulated in some cancers. In this study we examined the expression and oncogenic function of HOX genes in mesothelioma, a cancer arising from the pleura or peritoneum which is associated with exposure to asbestos. We tested the sensitivity of the mesothelioma-derived lines MSTO-211H, NCI-H28, NCI-H2052, and NCI-H226 to HXR9, a peptide antagonist of HOX protein binding to its PBX co-factor. Apoptosis was measured using a FACS-based assay with Annexin, and HOX gene expression profiles were established using RT-QPCR on RNA extracted from cell lines and primary mesotheliomas. The in vivo efficacy of HXR9 was tested in a mouse MSTO-211H flank tumor xenograft model. We show that HOX genes are significantly dysregulated in malignant mesothelioma. Targeting HOX genes with HXR9 caused apoptotic cell death in all of the mesothelioma-derived cell lines, and prevented the
Intestinal hormones are key regulators of digestion and energy homeostasis secreted by rare enteroendocrine cells. These cells produce over ten different hormones including GLP-1 and GIP peptides known to promote insulin secretion. To date, the molecular mechanisms controlling the specification of the various enteroendocrine subtypes from multipotent Neurog3+ endocrine progenitor cells, as well as their number, remain largely unknown. In contrast, in the embryonic pancreas, the opposite activities of Arx and Pax4 homeodomain transcription factors promote islet progenitor cells towards the different endocrine cell fates. In this study, we thus investigated the role of Arx and Pax4 in enteroendocrine subtype specification. The small intestine and colon of Arx- and Pax4-deficient mice were analyzed using histological, molecular, and lineage tracing approaches. We show that Arx is expressed in endocrine progenitors (Neurog3+) and in early differentiating (ChromograninA−) GLP-1-, GIP-, CCK-, Sct- Gastrin-
A screen for early markers of B-lymphocyte differentiation has identified a homeobox gene, denoted LH-2, that has a pattern of expression distinct from that of other related genes. The LH-2 cDNA sequence encodes a polypeptide of 426 amino acids that contains a homeodomain and two repeats of a cysteine-rich domain referred to as a LIM domain. The homeodomain of the LH-2 protein is related to that of other LIM/homeodomain proteins, most strikingly with that of the Drosophila apterous protein. Expression of LH-2 was found in B- and T-lymphoid cell lines. Expression in B-cell lines was highest in lines that represent early stages of differentiation, whereas in T-cell lines there was no clear correlation with the stage of differentiation. In embryonic and adult tissues, the highest level of LH-2 expression was found in discrete regions of the developing central nervous system, primarily in diencephalic and telencephalic structures, and in a subset of lymphoid tissues. The expression pattern and ...
Purpose: Disseminated retinoblastoma is still the major cause of mortality for this tumor worldwide. Research on the dissemination of this neoplasm has been hindered by the rarity of extraocular cases in developed countries. However, it would be of interest for developing countries. Using a prospective evaluation of a diagnostic clinical test, we evaluated the cone-rod homeobox transcription factor (CRX) as a new lineage-specific molecular marker for metastatic retinoblastoma and its usefulness as a tool for improving diagnostic accuracy and assessing the response to treatment and the patterns of disease dissemination in different clinical scenarios by the evaluation of minimal dissemination (MD) in extra-ocular sites.. Methods: To validate CRX mRNA as a marker, we evaluated its expression in 17 retinoblastoma primary tumors, two cell lines, and 47 specimens from other malignancies as negative controls. Seventeen consecutive patients with metastatic retinoblastoma (9 at diagnosis, 8 at relapse) ...
The homeobox containing transcription factor Nanog plays crucial roles in embryonic development/proliferation and/or maintenance of spermatogonial stem cells (SSCs) via interacting with transcription factors such as Oct4 and Sox2 in mammals. However, knowledge of its exact mechanistic pathways remains unexploited. Very little is known about teleost Nanog. Information on the Nanog gene of farmed rohu carp (Labeo rohita) is lacking. We cloned and characterized the Nanog gene of rohu carp to understand the expression pattern in early developmental stages and also deduced the genomic organization including promoter elements. Rohu Nanog (LrNanog) cDNA comprised an open reading frame of 1,161 nucleotides bearing a structural homeodomain; whereas, the genomic structure contained four exons and three introns suggesting that it is homologous to mammalian counterparts. Phylogenetically, it was closely related to freshwater counterparts. Protein sequence (386 AA of 42.65 kDa) comparison revealed its low similarity
The tissue-restricted GATA-4 transcription factor and Nkx2-5 homeodomain protein are two early markers of precardiac cells. Both are essential for heart formation, but neither can initiate cardiogenesis. Overexpression of GATA-4 or Nkx2-5 enhances cardiac development in committed precursors, suggesting each interacts with a cardiac cofactor. We tested whether GATA-4 and Nkx2-5 are cofactors for each other by using transcription and binding assays with the cardiac atrial natriuretic factor (ANF) promoter_the only known target for Nkx2-5. Co-expression of GATA-4 and Nkx2-5 resulted in synergistic activation of the ANF promoter in heterologous cells. The synergy involves physical Nkx2-5-GATA-4 interaction, seen in vitro and in vivo, which maps to the C-terminal zinc finger of GATA-4 and a C-terminus extension; similarly, a C-terminally extended homeodomain of Nkx2-5 is required for GATA-4 binding. Structure/function studies suggest that binding of GATA-4 to the C-terminus autorepressive domain of ...
Antennapedia Homeodomain Protein information including symptoms, causes, diseases, symptoms, treatments, and other medical and health issues.
Background: Survival of metastatic colorectal cancer (mCRC) patients has improved, but mainly for trial patients. New predictive and prognostic biomarkers validated in the general mCRC population are needed. Caudal-type homeobox 2 (CDX2) is an intestine-specific transcription factor with potential prognostic and predictive effect, but the importance in mCRC has not been fully investigated. Methods: Immunohistochemistry analysis of CDX2 was performed in a Scandinavian population-based cohort of mCRC (n = 796). Frequency, clinical and tumor characteristics, response rate, progression-free survival, and overall survival (OS) were estimated. Results: Loss of CDX2 expression was found in 87 (19%) of 452 stained cases, in 53% if BRAF mutated (BRAFmut) and in 9% if KRAS mutated (KRASmut). CDX2 loss was associated with microsatellite instability, BRAFmut, and poor differentiation and inversely associated with KRASmut. Patients with CDX2 loss received less first-line (53 vs. 64%, p = 0.050) and ...
Homeobox genes in the TALE class (TALE = Three Amino Acid Loop Extension) encode proteins with a 63-amino acid homeodomain, with the short extension located between alpha helices 1 and 2. The TALE group is sometimes given the rank of superclass and divided into several classes by the presence of distinct domains outside of the homeodomain - IRX, MKX, MEIS, PBC and TGIF (Bürglin 2005, Bürglin and Mukherjee 2007). We group these genes as one class divided into six gene families. There are 20 human TALE homeobox genes and 10 pseudogenes (Holland et al. 2007); amphioxus has 9 TALE homeobox genes (Takatori et al. 2008 ...
The HOX genes are a highly conserved family of homeodomain-containing transcription factors that specify cell identity in early development and, subsequently, in a number of adult processes including hematopoiesis. The dysregulation of HOX genes is associated with a number of malignancies including acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), where they have been shown to support the immortalization of leukemic cells both as chimeric partners in fusion genes and when overexpressed in their wild type form. This review covers our current understanding of the role of HOX genes in normal hematopoiesis, AML and ALL, with particular emphasis on the similarities and differences of HOX function in these contexts, their hematopoietic downstream genes targets and implications for therapy.Leukemia accepted article preview online, 5 December 2012; doi:10.1038/leu.2012.356.. ...
The Xenopus LIM-homeodomain protein Xlim5 regulates the differential adhesion properties of early ectoderm cells.: One of the earliest lineage restriction event
Correct identification of individual Hox proteins is an essential basis for their study in diverse research fields. Common methods to classify Hox proteins focus on the homeodomain that characterise homeobox transcription factors. Classification is hampered by the high conservation of this short domain. Phylogenetic tree reconstruction is a widely used but time-consuming classification method. We have developed an automated procedure, HoxPred, that classifies Hox proteins in their groups of homology. The method relies on a discriminant analysis that classifies Hox proteins according to their scores for a combination of protein generalised profiles. 54 generalised profiles dedicated to each Hox homology group were produced de novo from a curated dataset of vertebrate Hox proteins. Several classification methods were investigated to select the most accurate discriminant functions. These functions were then incorporated into the HoxPred program. HoxPred shows a mean accuracy of 97%. Predictions on the
Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a homeobox-containing transcription factor. This transcription factor functions as a negative regulator of epithelial cell growth in prostate tissue. Aberrant expression of this gene is associated with prostate tumor progression. Alternate splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jan 2012 ...
Here we demonstrate that TALE proteins have a key role in regulating regional epidermal barriers, at least partly through their differential regulation of LCE genes. Barrier qualities differ over the body surface, with the biggest measurable changes between internal epithelia that form the stratum corneum (e.g. tongue) and external skin (Marshall et al., 2000) (Fig. 1C). These differences probably permit the epithelia to respond appropriately to differences in aridity, microbial activity and requirement for flexibility in the different environments. However, these widely differing epithelia are derived from the same basal keratinocytes by region-specific differentiation programmes (Dhouailly et al., 2004). Based on work reported here, we propose that TALE proteins mediate these location-dependent barrier changes. In vitro, TALE proteins bind strongly to externally expressed LCE promoters but weakly to internally expressed LCE promoters. In vivo experiments confirm this result; we show that TALE ...
Nanog is a potential stem cell marker and is considered a regeneration factor during tissue repair. In the present study, we investigated expression patterns of nanog in the rat heart after acute myocardial infarction by semi-quantitative RT-PCR, immunohistochemistry and Western blot analyses. Our results show that nanog at both mRNA and protein levels is positively expressed in myocardial cells, fibroblasts and small round cells in different myocardial zones at different stages after myocardial infarction, showing a spatio-temporal and dynamic change. After myocardial infarction, the nanog expression in fibroblasts and small round cells in the infarcted zone (IZ) is much stronger than that in the margin zone (MZ) and remote infarcted zone (RIZ). From day 7 after myocardial infarction, the fibroblasts and small cells strongly expressed nanog protein in the IZ, and a few myocardial cells in the MZ and the RIZ and the numbers of nanog-positive fibroblasts and small cells reached the highest peak at 21
Fingerprint Dive into the research topics of The Drosophila homolog of Onecut homeodomain proteins is a neural- specific transcriptional activator with a potential role in regulating neural differentiation. Together they form a unique fingerprint. ...
Complex multicellularity requires elaborate developmental mechanisms, often based on the versatility of heterodimeric transcription factor (TF) interactions. Homeobox TFs in the TALE superclass are deeply embedded in the gene regulatory networks that orchestrate embryogenesis. Knotted-like homeobox (KNOX) TFs, homologous to animal MEIS, have been found to drive the haploid-to-diploid transition in both unicellular green algae and land plants via heterodimerization with other TALE superclass TFs, demonstrating remarkable functional conservation of a developmental TF across lineages that diverged one billion years ago. Here, we sought to delineate whether TALE-TALE heterodimerization is ancestral to eukaryotes. We analyzed TALE endowment in the algal radiations of Archaeplastida, ancestral to land plants. Homeodomain phylogeny and bioinformatics analysis partitioned TALEs into two broad groups, KNOX and non-KNOX. Each group shares previously defined heterodimerization domains, plant KNOX-homology in the
SUMMARY The even-skipped related genes (evx) encode homeodomain-containing transcription factors that play key roles in body patterning and neurogenesis in a wide array of Eumetazoa species. It is thought that the genome of the last common ancestor of Chordata contained a unique evx gene linked to a unique ancestral Hox complex. During subsequent evolution, two rounds of whole genome duplication followed by individual gene losses gave rise to three paralogs: evx1, evx2, and eve1. Then, eve1 was maintained in Actinopterygii lineage but not in Tetrapoda. To explain this discrepancy, we examined the expression patterns of the evx1 homologue, Xhox3, in Xenopus laevis and that of evx1 and eve1 in Danio rerio. We show here that Xhox3 is expressed in a manner that closely reflects the inferred expression pattern of the evx1 gene in the last common ancestor of Vertebrata (i.e., in gastrula, the central nervous system, the posterior gut, and the tip of the growing tail). Zebrafish evx1 and Xenopus Xhox3 ...
Abstract-Homeodomain-containing transcription factors are critical in the regulation of cell proliferation, differentiation, and migration, and they play an important role in organogenesis and pattern formation during embryogenesis. There is evidence that some of them are oncogenes or tumor suppressors. The cardiovascular system undergoes extensive remodeling during embryogenesis and disease states such as atherosclerosis and tumor-induced angiogenesis, and homeobox genes may play an important role in regulating these processes. Recently, homeobox genes have been detected in both vascular smooth muscle and endothelial cells, and they are implicated in pathological processes such as arterial restenosis after balloon angioplasty and tumor-induced angiogenesis. The cellular function of some of these genes is beginning to be elucidated. Therefore, we briefly review what is currently known about the involvement of homeobox transcription factors in both physiological and pathological vascular ...
The zinc finger E-box-binding transcription factor Zeb1 plays a pivotal role in the epithelial-mesenchymal transition. Numerous studies have focused on the molecular mechanisms by which Zeb1 contributes to this process. However, the functions of Zeb1 beyond the epithelial-mesenchymal transition remain largely elusive. Using a transdifferentiation system to convert mouse embryonic fibroblasts (MEFs) into functional neurons via the neuronal transcription factors achaete-scute family bHLH (basic helix-loop-helix) transcription factor1 (Ascl1), POU class 3 homeobox 2 (POU3F2/Brn2), and neurogenin 2 (Neurog2, Ngn2) (ABN), we found that Zeb1 was up-regulated during the early stages of transdifferentiation ...
cdx4, a caudal-related homeodomain-containing transcription factor, functions as a regulator of hox genes, thereby playing a critical role in anterior-posterior (A-P) patterning during embryogenesis. In zebrafish, homozygous deletion of the cdx4 gene results in a mutant phenotype known as kugelig, with aberrant A-P patterning and severe anemia characterized by decreased gata1 expression in the posterior lateral mesoderm. To identify pathways that interact with cdx4 during primitive hematopoiesis, we conducted a chemical genetic screen in the cdx4 mutant background for compounds that increase gata1 expression in cdx4 mutants. Among 2640 compounds that were tested, we discovered two compounds that rescued gata1 expression in the cdx4-mutant embryos. The strongest rescue was observed with bergapten, a psoralen compound found in bergamont oil. Another member of the psoralen family, 8-methoxypsoralen, was also found to rescue gata1 expression in cdx4-mutant embryos. The psoralen compounds also ...
sine oculis homeobox homolog 6 (Drosophila), sine oculis homeobox (Drosophila) homolog 6, Sine oculis homeobox homolog 6, Homeodomain protein OPTX2, Six9, Homeobox protein SIX6, MCOPCT2, Optic homeobox 2, OPTX2, SIX9, SIX6 ...
GABA is the key inhibitory neurotransmitter in the cortex but regulation of its synthesis during forebrain development is poorly understood. In the telencephalon, members of the distal-less (Dlx) homeobox gene family are expressed in, and regulate the...
This gene encodes a member of the LIM/homeodomain family of transcription factors. The encoded protein binds to the enhancer region of the insulin gene, among others, and may play an important role in regulating insulin gene expression. The encoded protein is central to the development of pancreatic cell lineages and may also be required for motor neuron generation. Mutations in this gene have been associated with maturity-onset diabetes of the young. [provided by RefSeq, Jul 2008 ...
All isoforms are required for patterning of the embryonic cuticle. Acts with exd to delimit the eye field and prevent inappropriate eye development. Isoforms that carry the homeodomain are required for proper localization of chordotonal organs within the peripheral nervous system and antennal identity; required to activate antennal-specific genes, such as sal and to repress the leg-like expression of dac. Necessary for the nuclear localization of the essential HOX cofactor, extradenticle (exd). Both necessary and sufficient for inner photoreceptors to adopt the polarization-sensitive dorsal rim area (DRA) of the eye fate instead of the color-sensitive default state. This occurs by increasing rhabdomere size and uncoupling R7-R8 communication to allow both cells to express the same opsin rather than different ones as required for color vision.
Hox as well as Meis proteins are known to bind DNA as heterodimers with members of the Pbx family, and it is believed that such complexes mediate the in vivo functions of Hox and Meis. To begin exploring the role of hoxb1b and meis3 in vertebrate development, we isolated and characterized a zebrafish pbx cDNA which encodes a novel member of the pbx family, which we called pbx4. In situ analysis revealed that pbx4 RNA is maternally deposited and is detected throughout the zebrafish embryo during blastula stages. It becomes excluded from ventroanterior structures at late gastrula stages and is detected within the developing central nervous system during segmentation stages. pbx4 expression overlaps with that of hoxb1b and meis3, in the region of the presumptive caudal hindbrain during gastrula stages. In vitro binding experiments revealed that Pbx4/Meis3 and Pbx4/Hoxb1b, as well as a novel trimeric complex containing Pbx4, Meis3 and Hoxb1b form in vitro. Thus, protein complexes of different combinations
Homeobox protein Meis2 is a protein that in humans is encoded by the MEIS2 gene.[5][6] This gene encodes a homeobox protein belonging to the TALE (three amino acid loop extension) family of homeodomain-containing proteins. TALE homeobox proteins are highly conserved transcription regulators, and several members have been shown to be essential contributors to developmental programs. Multiple transcript variants encoding distinct isoforms have been described for this gene.[6] ...
Although Hox genes specify the anterior-posterior difference in the differentiation of neuronal subtypes, their mode of action is not entirely understood. Using two subtypes of the touch receptor neurons (TRNs) in C. elegans, we found that posterior induction underlies the Hox control of terminal neuronal differentiation. The anterior TRNs maintain a default TRN state, whereas the posterior TRNs undergo further morphological and transcriptional differentiation because of the posterior Hox proteins, mainly EGL-5/Abd-B. Misexpression of EGL-5 in the anterior TRNs cause them to differentiate more like the posterior cells. Finally, EGL-5 is required for subtype-specific circuit formation by acting in both the sensory neuron and downstream interneuron to promote functional connectivity. Our studies suggest that Hox proteins regulate subtype diversification of neurons that share the same general cell fate.. Zheng C, Diaz-Cuadros M, and Chalfie M. Hox Genes Promote Neuronal Subtype Diversification ...
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The importance of Msx genes in regulating development of ocular, neuronal, cardiac, ectodermal and oro-craniofacial structures has been well established. Previous studies have shown that Msx proteins regulate gene transcription predominantly through repression by forming transcriptionally inactive heteromeric complexes. In contrast to their known suppressor activities, gene expression studies using either the gain-of-function or the loss-of-function mutants revealed many gene targets whose expression requires functional Msx proteins. Here we present data demonstrating for the first time that Msx proteins function as activators of transcription by controlling the intracellular distribution and by modulating the transcriptional activity of partnering molecules. Msx proteins activate the Hsp70 promoter through a mechanism in which Msx protein physically interacts with and modify Heat shock transcriptional factors (Hsfs) to facilitate their nuclear translocation, accumulation and subsequent ...
Shop BarH-like 2 homeobox protein ELISA Kit, Recombinant Protein and BarH-like 2 homeobox protein Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
Using Hox transcription factors as a paradigm, Graba-Saurin team study how regulation of protein interaction controls the assembly of multiprotein complexes and how this generates specificity and diversity in gene regulation (Drosophila melanogaster).
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Homeobox (HOX) genes are contributed in the genetic control of development of the body plan, pattern formation, and cell fate determination and the other several key developmental processes. HOX genes are also known as selector genes because expression within a given section of the embryo will cause its cells to choose ...
I investigate molecular mechanisms that are at the basis of Hox transcription factor specificity by implementing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in Drosophila.
Sirt1 was previously shown to interact with the PcG repressive complex PRC4, which is expressed specifically in stem and cancer cells (Kuzmichev et al., 2005). Notably, the formation of Sirt1-containing PcG complexes was enhanced in the presence of oxidative stress (OHagan et al., 2011); their physiological relevance, however, remained elusive. Our data now provide evidence that Sirt1 can directly modulate the expression of PcG target genes at the chromatin level, which may at least in part control maintenance of HSCs. In agreement with the limited expression pattern of PRC4, we found that HSPCs were more susceptible to the consequences of Sirt1 loss than more differentiated hematopoietic cell subsets (Figs. 1 F and 5 G). Fittingly, the effect of Sirt1 on Hox gene regulation was limited to the HSPC-associated Hox-A cluster genes Hoxa9 and Hoxa10, and increased H4K16 acetylation in the absence of Sirt1 appeared specific to the Hox-A cluster (Fig. 7 B). Notably, increased H4 acetylation was not ...
bHLH transcription factors have common roles in inducing neuronal differentiation, but distinct roles in neuronal subtype specification, functions that are contingent on developmental context (Parras et al., 2002; Nakada et al., 2004a; Powell et al., 2004; Reeves and Posakony, 2005). To determine Atoh1-specific targets, we first identified transcripts specific to the Atoh1 lineage and not common to the neighboring dorsal Neurog1 lineage. Significantly, we identified five new Atoh1-specific targets and their responsive enhancers using a combination of microarray expression data, ChIP-seq experiments, and enhancer-reporter assays.. Previously, known direct targets of Atoh1 in vivo in the developing neural tube or cerebellum included the homeodomain transcription factors, Barhl1 and Barhl2 (Saba et al., 2005; Kawauchi and Saito, 2008), the Sonic hedgehog transcriptional effector, Gli2 (Flora et al., 2009), and Atoh1 itself (Helms et al., 2000). The direct Atoh1 targets identified here have diverse ...
Hiroi N, Kino T, Bassett M, Rainey WE, Phung M, Abu-Asab M, Fojo T, Briata P, Chrousos GP, Bornstein SR (May 2003). Pituitary homeobox factor 1, a novel transcription factor in the adrenal regulating steroid 11beta-hydroxylase. Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Metabolisme. 35 (5): 273-8. doi:10.1055/s-2003-41301. PMID 12915995 ...
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