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

Oct-2, a POU homeodomain protein expressed primarily in B cells, is a powerful transcriptional activator that binds to DNA at sites appropriately placed for major effects on immunoglobulin gene expression. Our examination of B cell development and function in Oct-2 null mice did not support an essential role for Oct-2 early in B cell development. Rather, Oct-2 was required later, when B cells were induced to differentiate to antibody-secreting cells. We show here that Oct-2 is not required for normal immunoglobulin production by mature B lymphocytes. Instead, it is essential for a normal proliferative response to polyclonal mitogens. Responses to signals from activated T cells are unaffected. The requirement for Oct-2 maps to an early activation step in G1, during which B cells make the commitment to progress through the cell cycle and to divide.
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PMID:Oct-2 is required early in T cell-independent B cell activation for G1 progression and for proliferation. 760 Feb 91

SWI5 encodes a zinc-finger protein required for expression of the yeast HO gene. Using Swi5 protein that was purified from a bacterial expression system, we previously isolated a yeast factor that stimulates binding of Swi5 to the HO promoter. N-terminal amino acid sequence analysis identified the Swi5 stimulatory factor as the product of the GRF10 gene, which encodes a yeast homeodomain protein. GRF10, also known as PHO2 and BAS2, is a transcriptional activator of the PHO5 acid phosphatase gene and the HIS4 histidine biosynthesis gene. Grf10 protein purified from a bacterial expression system binds DNA cooperatively with Swi5 in vitro. Analysis of disassociation rates indicates that the Grf10-Swi5-DNA complex has a longer half-life than protein-DNA complexes that contain only Swi5 or Grf10. Finally, we show that HO expression is reduced in yeast strains containing grf10 null mutations and that full expression of a heterologous promoter containing a SWI5-dependent HO upstream activation sequence element requires GRF10.
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PMID:The Swi5 zinc-finger and Grf10 homeodomain proteins bind DNA cooperatively at the yeast HO promoter. 790 83

Insulin promoter factor 1 (IPF1), a member of the homeodomain protein family, serves an early role in pancreas formation, as evidenced by the lack of pancreas formation in mice carrying a targeted disruption of the IPF1 gene [Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. (1994) Nature (London) 371, 606-609]. In adults, IPF1 expression is restricted to the beta-cells in the islets of Langerhans. We report here that IPF1 induces expression of a subset of beta-cell-specific genes (insulin and islet amyloid polypeptide) when ectopically expressed in clones of transformed pancreatic islet alpha-cells. In contrast, expression of IPF1 in rat embryo fibroblasts factor failed to induce insulin and islet amyloid polypeptide expression. This is most likely due to the lack of at least one other essential insulin gene transcription factor, the basic helix-loop-helix protein Beta 2/NeuroD, which is expressed in both alpha- and beta-cells. We conclude that IPF1 is a potent transcriptional activator of endogenous insulin genes in non-beta islet cells, which suggests an important role of IPF1 in beta-cell maturation.
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PMID:Induction of insulin and islet amyloid polypeptide production in pancreatic islet glucagonoma cells by insulin promoter factor 1. 879 46

The pancreatic beta cell is the major source of circulating insulin in adult mammals. In the multistep process of insulin synthesis it is initiation of transcription that restricts insulin synthesis to the beta cell since all subsequent steps can be performed by other cell types. Many of the transcription factors that bind to the insulin promoter and activate insulin gene transcription have been isolated. Some of these factors are restricted in their expression pattern, but so far no truly beta cell-specific transcriptional activator has been found. Since different transcription factors synergize to activate insulin gene transcription, cell-specific transcription of insulin is probably realized through the interactions of a unique set of regulatory proteins in the beta cell. The same transcription factors that regulate insulin gene transcription in the adult beta cell are involved in determining cell differentiation during pancreatic development. The endocrine and exocrine pancreas form from the gut endoderm as a dorsal and a ventral bud which later fuse to build a single organ. The homeodomain protein PDX-1, an insulin gene transcription factor, is uniformly expressed in the early pancreatic bud, and null mutation of PDX-1 in mice results in a failure of the pancreatic bud to grow and differentiate. Other transcription factors, such as the helix-loop-helix protein Beta-2 and the homeodomain protein Nkx 6.1, show a restricted pattern of expression during embryogenesis and in the mature islet. Those proteins may serve a dual role for the organism: during embryogenesis they may determine islet cell differentiation and in the adult they may ensure tissue-specific expression of the islet cell hormones. A better understanding of the factors involved in insulin gene transcription and islet cell differentiation will ultimately provide the basis for novel therapy of diabetes.
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PMID:The beta cell transcription factors and development of the pancreas. 918 74

We have recently demonstrated that the retinoblastoma family of negative cell cycle regulators can form complexes with a class of developmental factors which contain paired-like (PL) homeodomains (Wiggan et al. [1998] Oncogene 16:227-236). Our screens led to the isolation of a novel PL-homeodomain protein which had been isolated independently by another group and called Alx-4 (Qu et al. [1997] Development 124:3999-4008). Mice homozygous for a targeted null mutation of Alx-4 have several abnormalities, including preaxial polydactyly, suggesting that Alx-4 plays a role in pattern formation in limb buds. In data that we present here, we show that Alx-4 is expressed in mesenchymal condensations of a diverse group of tissues whose development is dependent on epithelial-mesenchymal interactions, many of which are additionally dependent on expression of the HMG-box-containing protein, LEF-1. Alx-4-expressing tissues include osteoblast precursors of most bones, the dermal papilla of hair and whisker follicles, the dental papilla of teeth, and a subset of mesenchymal cells in pubescent mammary glands. We show further that Alx-4 strongly activates transcription from a promoter containing the homeodomain binding site, P2. Optimal activation requires specific sequences in the N-terminal portion of Alx-4 as well as a proline-rich region downstream of the PL-homeodomain, but not the paired-tail at the C terminus. Taken together, our results demonstrate that Alx-4 is a potent transcriptional activator that is expressed at sites of epithelial-mesenchymal interactions during murine embryonic development.
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PMID:Alx-4, a transcriptional activator whose expression is restricted to sites of epithelial-mesenchymal interactions. 978 16

Dharma/Bozozok (Dha/Boz) is a homeodomain protein containing an Engrailed homology (Eh) 1 repressor motif. It is important in zebrafish dorsal organizer formation. Dha/Boz interacted with a co-repressor Groucho through the Eh1 motif. Expression of a Dha/Boz fused to the transcriptional activator VP16 repressed dorsal axis formation and the expression of organizer genes but led to the dorsal expansion of expression of the homeobox gene vox/vega1, indicating that Dha/Boz functions as a transcriptional repressor for dorsal axis formation. We also isolated a novel homeobox gene, ved, whose expression was negatively regulated by dha/boz. ved's sequence and expression profile were similar to those of vox/vega1 and vent/vega2. Like Vox/Vega1 and Vent/Vega2, Ved acted as a transcriptional repressor. The combined inhibition of ved, vox/vega1, and vent/vega2, by antisense morpholino injection, strongly dorsalized the embryos and elicited ventral expansion of organizer gene expression, compared with the effect of inhibiting each of these genes alone. These results suggest that ved is a target for the repressor Dha/Boz. Ved functions redundantly with vox/vega1 and vent/vega2 to restrict the organizer domain.
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PMID:A novel repressor-type homeobox gene, ved, is involved in dharma/bozozok-mediated dorsal organizer formation in zebrafish. 1235 Nov 76

In Drosophila, cell-fate determination of all neuroectoderm-derived glial cells depends on the transcription factor Glial cells missing (GCM), which serves as a binary switch between the neuronal and glial cell fates. Because the expression of GCM is restricted to the early phase of glial development, other factors must be responsible for the terminal differentiation of glial cells. Expression of three transcription factors, Reversed Polarity (REPO), Tramtrack p69 (TTK69) and PointedP1 (PNTP1), is induced by GCM in glial cells. REPO is a paired-like homeodomain protein, expressed exclusively in glial cells, and is required for the migration and differentiation of embryonic glial cells. To understand how REPO functions in glial terminal differentiation, we have analyzed the mechanism of gene regulation by REPO. We show that REPO can act as a transcriptional activator through the CAATTA motif in glial cells, and define three genes whose expression in vivo depends on REPO function. In different types of glial cells, REPO can act alone, or cooperate with either TTK69 or PNTP1 to regulate different target genes. Coordination of target gene expression by these three transcription factors may contribute to the diversity of glial cell types. In addition to promoting glial differentiation, we found that REPO is also necessary to suppress neuronal development, cooperating with TTK69. We propose that REPO plays a key role in both glial development and diversification.
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PMID:Drosophila homeodomain protein REPO controls glial differentiation by cooperating with ETS and BTB transcription factors. 1270 56

TLX1/HOX11, a DNA-binding homeodomain protein, was originally identified by virtue of its aberrant expression in T-cell leukemia and subsequently found to be crucial for normal spleen development. The precise mechanism of TLX1 function remains poorly understood, although it is known that it can act as both a transcriptional activator and repressor and can downregulate the Aldh1a1 gene in embryonic mouse spleen. Using a whole-genome PCR approach, we show here that TLX1 protein directly interacts with pericentromeric human satellite 2 DNA sequences. Such DNA is known to localize to heterochromatin, which among other roles has been implicated in gene silencing. The interaction was confirmed in vitro and in vivo by gel retardation and chromatin immunoprecipitation assays involving satellite 2 DNA, which contained sequences resembling TLX1 binding sites. Using immunofluorescence microscopy, TLX1 demonstrated a punctate pattern of staining in the nuclei of leukemic T-cells (ALL-SIL). Double labelling indicated that TLX1 colocalized with the centromeric protein CENP-B, demonstrating that the TLX1 foci corresponded to clusters of centromeric DNA. The novel interaction of TLX1 with constitutive heterochromatin adds an additional level of complexity to the intracellular functions of this transcriptional regulator and may have relevance to its roles in transcriptional repression and T-cell immortalization.
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PMID:The nuclear oncoprotein TLX1/HOX11 associates with pericentromeric satellite 2 DNA in leukemic T-cells. 1635 34

The transcription factor Otx2 is expressed throughout the anterior neuroectoderm and is required for the formation of all forebrain- and midbrain-derived structures. The molecular determinants that cooperate with Otx2 to subdivide its expression domain into distinct functional units are, however, poorly understood at present. We show here that the TALE-homeodomain protein Meis2 is expressed in the chick tectal anlage and is both necessary and sufficient for tectal development. Unlike known tectum-inducing genes, the ability of Meis2 to initiate tectal development does not involve the formation of a secondary midbrain-hindbrain boundary organizer, but instead requires direct interaction with Otx2. Using an Otx2-dependent reporter assay we demonstrate that Meis2 competes with the Groucho co-repressor Tle4 (Grg4) for binding to Otx2 and thereby restores Otx2 transcriptional activator function. Together, our data suggest a model in which the balance between a co-repressor and a co-activator, which compete for binding to Otx2 in the mesencephalic vesicle, provides spatial and temporal control over tectal development. Controlled formation of Meis2-containing higher order protein complexes might thus serve as a general mechanism to achieve subdivision of the anterior neuroectoderm into distinct functional units during embryogenesis.
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PMID:Meis2 competes with the Groucho co-repressor Tle4 for binding to Otx2 and specifies tectal fate without induction of a secondary midbrain-hindbrain boundary organizer. 1973 26


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