Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new maize homeobox gene was isolated by screening a lambda gt11 expression library with the 26 bp Shrunken feedback control element. Zmhox1a (Zea mays homeobox) is an unidentified maize gene mapping to the long arm of chromosome 8. It is a member of a new class of maize homeobox genes only distantly related to the Knotted class. The 3.1 kb Zmhox1a transcript can be detected in different maize tissues and encodes a polypeptide of 719 amino acids. Western blotting experiments detect the native 112 or 115 kDa protein in nuclear protein extracts, the nuclear localization being compatible with a function in transcriptional control. No Zmhox1a protein is detected in maize roots despite the presence of the Zmhox1a transcript; this may indicate a post-transcriptional control mechanism. A highly acidic central region of the Zmhox1a polypeptide implies a transcriptional activator function. The carboxy-terminal part of the maize homeodomain protein is related to the human Oct2 transcription factor, but homology to the POU specific domain is restricted to the POU-B subdomain. It was confirmed by DNase I footprinting experiments that DNA binding of the Zmhox1a homeodomain was at three sites flanking the TATA-box of the Shrunken promoter.
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PMID:Zmhox1a, the product of a novel maize homeobox gene, interacts with the Shrunken 26 bp feedback control element. 135 14

The homeodomain is a DNA-binding domain present in a large family of eukaryotic regulatory proteins. Homeodomain proteins have been shown to play key roles in controlling developmental programs in various organisms. Here we report the isolation and characterisation of a homeobox gene from Arabidopsis thaliana designated ATK1. The gene was isolated using as a probe the homeobox domain of the KN1 gene from maize. The homeodomain of ATK1 is highly homologous to the homeodomain of the KN1 gene of maize (81%) but shows only poor homology outside the homeodomain. Therefore ATK1 is probably not the Arabidopsis homologue of the KN1 gene from maize. It contains the four invariant amino acid residues present in the recognition helix 3 of all other homeodomain proteins. Outside the homeodomain a region rich in aspartate and glutamate residues is found suggesting that ATK1 is a transcriptional activator. The gene contains four introns which is similar in the KN1 gene of maize and the Osh1 gene of rice. Primer extension reveals the presence of two transcription initiation sites. The leader sequence of the genuine transcript is 342 nucleotides long and contains two upstream open reading frames. ATK1 is strongly expressed in the shoot apex of seedlings, while in mature plants the gene is primarily expressed in flowers and inflorescence stems. Such an expression pattern is reminiscent of that of the KN1 gene of maize and therefore ATK1 could similarly be involved in determining cell fate.
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PMID:The homeobox gene ATK1 of Arabidopsis thaliana is expressed in the shoot apex of the seedling and in flowers and inflorescence stems of mature plants. 764 3

We have screened a cDNA library prepared from tomato (Lycopersicon esculentum Mill. cv. VFNT Cherry) shoot tips for homeobox-containing clones. The isolated cDNA clone THOM1 (tomato homeobox gene 1) contains a homeobox, a leucine zipper motif and and an acidic region. These features support the hypothesis that the THOM1 gene product acts as a transcriptional activator. THOM1 is highly expressed in the vegetative shoot apical meristem, the floral meristem and axillary meristems. Young derivatives of these meristems show similar levels of THOM1 transcripts which decrease with increasing age of the respective tissue. The THOM1 gene is located in the centromere region of chromosome 1 and belongs to a small gene family of the tomato genome.
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PMID:Isolation and characterization of the tomato homeobox gene THOM1. 776 50

HNF1 is a transcriptional activator of many hepatic genes including albumin, alpha1-antitrypsin, and alpha- and beta-fibrinogen. It is related to the homeobox gene family and is predominantly expressed in liver and kidney. Mice lacking HNF1 fail to thrive and die around weaning after a progressive wasting syndrome with a marked liver enlargement. The transcription rate of genes like albumin and alpha1-antitrypsin is reduced, while the gene coding for phenylalanine hydroxylase is totally silent, giving rise to phenylketonuria. Mutant mice also suffer from severe Fanconi syndrome caused by renal proximal tubular dysfunction. The resulting massive urinary glucose loss leads to energy and water wasting. HNF1-deficient mice may provide a model for human renal Fanconi syndrome.
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PMID:Hepatocyte nuclear factor 1 inactivation results in hepatic dysfunction, phenylketonuria, and renal Fanconi syndrome. 859 44

Spemann's organizer develops in response to dorsal determinants that act via maternal components of the wnt pathway. The function of siamois, a wnt-inducible homeobox gene, in Spemann's organizer development was examined by fusion of defined transcriptional regulatory domains to the siamois homeodomain. Similar to native siamois, a VP16 activator fusion induced axis formation, indicating that siamois functions as a transcriptional activator in axis induction. Fusion of the engrailed repressor generated a dominant inhibitor that blocked axis induction by Xwnt8, beta-catenin, and siamois, and repressed wnt activation of the goosecoid promoter. Dorsal injection of the engrailed-siamois fusion resulted in complete inhibition of dorsal development and organizer gene expression, an effect rescued by siamois, but not by Xwnt8 or beta-catenin. Thus, as a zygotic mediator of maternal dorsal signals, siamois function is required for development of Spemann's organizer.
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PMID:Siamois is required for formation of Spemann's organizer. 937 92

We have studied the role of the activin immediate-early response gene Mix.1 in mesoderm and endoderm formation. In early gastrulae, Mix.1 is expressed throughout the vegetal hemisphere, including marginal-zone cells expressing the trunk mesodermal marker Xbra. During gastrulation, the expression domains of Xbra and Mix.1 become progressively exclusive as a result of the establishment of a negative regulatory loop between these two genes. This mutual repression is important for the specification of the embryonic body plan as ectopic expression of Mix.1 in the Xbra domain suppresses mesoderm differentiation. The same effect was obtained by overexpressing VP16Mix.1, a fusion protein comprising the strong activator domain of viral VP16 and the homeodomain of Mix.1, suggesting that Mix.1 acts as a transcriptional activator. Mix.1 also has a role in endoderm formation. It cooperates with the dorsal vegetal homeobox gene Siamois to activate the endodermal markers edd, Xlhbox8 and cerberus in animal caps. Conversely, vegetal overexpression of enRMix.1, an antimorphic Mix.1 mutant, leads to a loss of endoderm differentiation. Finally, by targeting enRMix.1 expression to the anterior endoderm, we could test the role of this tissue during embryogenesis and show that it is required for head formation.
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PMID:A role for the vegetally expressed Xenopus gene Mix.1 in endoderm formation and in the restriction of mesoderm to the marginal zone. 960 20

We report here the characterization of the Drosophila homolog of the onecut homeobox gene, which encodes a protein product with one cut domain and one homeodomain. We present evidence that D-Onecut can bind to similar DNA sequences with high specificity and affinity as other Onecut proteins through the highly conserved cut domain and homeodomain. Interestingly, the cut domain alone can mediate DNA-binding, but the homeodomain cannot. However, depending upon the promoter context, we observed cooperative interactions between the two domains to confer high DNA-binding affinity and specificity. D-Onecut appears to be a moderate transcriptional activator and functions as a nuclear protein in neuronal tissues of both the CNS and PNS during development and in the adult. In the eye, D-Onecut expression is independent of glass, a transcriptional regulator of R cell differentiation. Taken together, our results suggest a role for D-Onecut in the regulation of some aspects of neural differentiation or maintenance. In support of this notion, overexpression of a putative dominant negative form of D-Onecut during eye development does not affect early cell fate specification, but severely affects photoreceptor differentiation.
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PMID:The Drosophila homolog of Onecut homeodomain proteins is a neural-specific transcriptional activator with a potential role in regulating neural differentiation. 1102 7

The caudal homeobox gene Cdx-2 is a transcriptional activator for approximately a dozen genes specifically expressed in pancreatic islets and intestinal cells. It is also involved in preventing the development of colorectal tumors. Studies using "knockout" approaches demonstrated that Cdx-2 is haplo-insufficient in certain tissues including the intestines but not the pancreatic islets. The mechanisms, especially transcription factors, which regulate Cdx-2 expression, are virtually unknown. We found previously that Cdx-2 expression could be autoregulated in a cell type-specific manner. In this study, we located an octamer (OCT) binding site within the mouse Cdx-2 gene promoter. This site, designated as Cdx-2(P)OCT, is involved in the expression of the Cdx-2 promoter. Both pancreatic and intestinal cell lines were found to express a number of POU (OCT binding) homeodomain proteins examined by electrophoretic mobility shift assay. However, it appears that Cdx-2(P)OCT interacts only with OCT1 in the nuclear extracts of the intestinal cell lines examined, although it interacts with OCT1 and at least two other POU proteins that are to be identified in the pancreatic InR1-G9 cell nuclear extract. Co-transfecting OCT1 cDNA but not five other POU gene cDNAs activates the Cdx-2 promoter in the pancreatic InR1-G9 and the intestinal Caco-2 cell lines. In contrast, Cdx-2(P)OCT cannot act as an enhancer element if it is fused to a thymidine kinase promoter. Furthermore, Cdx-2(P)OCT-thymidine kinase fusion promoters cannot be activated by OCT1 co-transfection. Cell type-specific expression, cell type-specific binding affinity of POU proteins to the cis-element Cdx-2(P)OCT, and the DNA content-dependent activation of Cdx-2 promoter via Cdx-2(P)OCT by OCT1 suggest that POU proteins play important and complicated roles in modulating Cdx-2 expression in cell type-specific manners.
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PMID:Pou homeodomain protein OCT1 is implicated in the expression of the caudal-related homeobox gene Cdx-2. 1127

We have isolated the Arabidopsis thaliana homeobox gene Athb-12, determined its structure and activation domain, demonstrated that its promoter is inducible in response to abscisic acid (ABA) treatment, and characterized the cellular distribution of its transcripts. The single intron of the gene interrupted the leucine-zipper domain region. The 5' regulatory region of Athb-12 can drive beta-glucuronidase (GUS) expression in tobacco transgenic plants. Athb-12 gene expression was further examined using in situ hybridization to determine the cellular distribution of Athb-12 transcripts during ABA induction. A complex pattern of Athb-12 expression was observed, often associated with regions of developing vascular tissues. Analysis of chimeras constructed from Athb-12 and the DNA-binding domain of the Saccharomyces cerevisiae transcription factor GAL4 revealed that the activation domain of Athb-12 lies in the C-terminal region (amino acids 180 to 235). Taken together, our data suggest that Athb-12 is a transcriptional activator important in regulating certain developmental processes as well as in the plant's response to water stress involving ABA-mediated gene expression.
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PMID:Structure and expression of the Arabidopsis thaliana homeobox gene Athb-12. 1137 82

Six3 is a vertebrate homeobox gene that is expressed in the anterior neural plate and eye anlage. We overexpressed a dominant transcriptional activator or repressor form of Six3 in zebrafish embryos to analyze their effect on eye and forebrain formation. RNA injection of the activator form of Six3 into zebrafish embryos caused reduction of the expression domains for rx2, pax2, and emx1 in the anterior neural plate, resulting in eye and forebrain hypoplasia. On the other hand, overexpression of the repressor form of Six3 or wild-type Six3 showed phenotypes opposite to those of the activator form. We found that Six3 has eh1-related motifs, motifs crucial for transcriptional repression function of Drosophila engrailed which plays a role in tethering the Groucho corepressor to the promoters. We isolated one of the zebrafish Groucho family genes, grg3, and demonstrated an interaction between Six3 and Grg3 using yeast two-hybrid analysis. Point-mutations in the eh1-related motifs in Six3 reduced both its eye and forebrain enlarging activities and its interaction with Grg3. These results strongly argue that Six3 functions as a Groucho-dependent repressor in eye and forebrain formation. Furthermore, zebrafish Six2 and Six4 also interacted with Grg3, implying a conserved function among the Six family proteins as transcriptional repressors.
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PMID:The homeobox protein Six3 interacts with the Groucho corepressor and acts as a transcriptional repressor in eye and forebrain formation. 1140 94


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