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Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transforming proteins encoded by the adenovirus E1A gene bind to a 300-kDa cellular product, p300, via the N-terminal E1A sequences. Residues important for p300 binding are required for the transformation function of E1A and for other E1A-mediated gene-regulating functions, including activation of cell cycle-regulated products and repression of tissue-specific enhancer activity. Recent evidence indicates that p300 is a DNA-binding protein with specific affinity for known enhancer motifs, suggesting that p300 may be a component of transcription factor complexes. The possibility that upstream element-binding factors might interact with basal transcription factors led us to investigate whether p300 interacts, directly or indirectly, with the TATA-binding protein (TBP). We report here that TBP-specific immunoprecipitations show a 300-kDa protein co-precipitating with TBP. This protein is lost from the precipitated material if the lysates are boiled in sodium dodecyl sulfate prior to immunoprecipitation, implying that its presence does not result from non-specific antibody cross-reactivity, but is dependent on specific association with TBP. The TBP-associated 300-kDa protein and p300 originally defined by E1A association show indistinguishable partial proteolytic digest patterns, indicating that these are identical or closely related species. Moreover, p300-specific complexes and TBP-specific complexes include at least two additional common polypeptide species, phosphoproteins of 64 and 59 kDa. These results suggest that p300 interacts with TBP, possibly through intermediate protein-protein associations. They thus provide additional biochemical evidence for postulated protein-protein interactions between upstream regulatory factors and the basal transcriptional machinery.
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PMID:p300, and p300-associated proteins, are components of TATA-binding protein (TBP) complexes. 850 84

The TATA-less murine Msx1 promoter contains two Msx1-binding motifs, located at -568 to -573 and +25 to +30, and is subject to potent autorepression [Takahashi, Guron, Shetty, Matsui and Raghow (1997) J. Biol. Chem. 272, 22667-22678]. To investigate the molecular mechanism by which Msx1 represses the activity of its own promoter, we transfected C2C12 myoblasts with Msx1-promoter-luciferase constructs and assessed reporter gene activity, with and without the exogenous expression of Msx1. We demonstrate that Msx1-mediated autorepression remained unaffected, regardless of the presence or absence of the Msx1 recognition motifs on the promoter. Furthermore, graded exogenous expression of TATA-binding protein (TBP), Sp1 or cAMP-response-element-binding protein-binding protein (CBP/p300) could counteract the autoinhibitory activity of Msx1. Finally, we demonstrate that Msx1 protein can be immunoprecipitated in a multiprotein complex containing TBP, Sp1 and CBP/p300. We hypothesize that the interaction of Msx1 protein with one or more ubiquitous or tissue-restricted transcription factors mediates transcriptional autorepression of the Msx1 gene.
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PMID:Transcriptional autorepression of Msx1 gene is mediated by interactions of Msx1 protein with a multi-protein transcriptional complex containing TATA-binding protein, Sp1 and cAMP-response-element-binding protein-binding protein (CBP/p300). 1021 16

Tissue-specific expression of the alpha-subunit gene of glycoprotein hormones involves an enhancer element designated the pituitary glycoprotein basal element, which interacts with the LIM homeodomain transcription factor, Lhx2. In the present studies we have explored the function of the LIM domain of Lhx2 in stimulating alpha-subunit transcription. When fused to the GAL4 DNA-binding domain, the LIM domain of Lhx2 was shown to contain a transcriptional activation domain. Furthermore, in the context of an alpha-subunit reporter gene in which a GAL4-binding site replaced the pituitary glycoprotein basal element, the LIM domain enhanced both basal and Ras-mediated transcription. In addition, a synergistic response to Ras activation was observed when the Lhx2 LIM domain and the transactivation domain of Elk1 are directed to a minimal reporter gene. A yeast two-hybrid screen identified the recently described melanocyte-specific gene-related gene 1 (MRG1) as an Lhx2 LIM-interacting protein. MRG1 was shown to bind Lhx2 in vitro, and a co-immunoprecipitation assay provided evidence that endogenous MRG1 forms a complex with Lhx2 in alphaT3-1 cells. Expression of MRG1 in alphaT3-1 cells enhanced alpha-subunit reporter gene activity. MRG1 was also shown to bind in vitro to the TATA-binding protein and the transcriptional coactivator, p300. These data suggest a model in which the Lhx2 LIM domain activates transcription through interaction with MRG1 leading to recruitment of p300/CBP and the TATA-binding protein.
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PMID:MRG1 binds to the LIM domain of Lhx2 and may function as a coactivator to stimulate glycoprotein hormone alpha-subunit gene expression. 1059

The state of chromatin (the packaging of DNA in eukaryotes) has long been recognized to have major effects on levels of gene expression, and numerous chromatin-altering strategies-including ATP-dependent remodeling and histone modification-are employed in the cell to bring about transcriptional regulation. Of these, histone acetylation is one of the best characterized, as recent years have seen the identification and further study of many histone acetyltransferase (HAT) proteins and their associated complexes. Interestingly, most of these proteins were previously shown to have coactivator or other transcription-related functions. Confirmed and putative HAT proteins have been identified from various organisms from yeast to humans, and they include Gcn5-related N-acetyltransferase (GNAT) superfamily members Gcn5, PCAF, Elp3, Hpa2, and Hat1: MYST proteins Sas2, Sas3, Esa1, MOF, Tip60, MOZ, MORF, and HBO1; global coactivators p300 and CREB-binding protein; nuclear receptor coactivators SRC-1, ACTR, and TIF2; TATA-binding protein-associated factor TAF(II)250 and its homologs; and subunits of RNA polymerase III general factor TFIIIC. The acetylation and transcriptional functions of these HATs and the native complexes containing them (such as yeast SAGA, NuA4, and possibly analogous human complexes) are discussed. In addition, some of these HATs are also known to modify certain nonhistone transcription-related proteins, including high-mobility-group chromatin proteins, activators such as p53, coactivators, and general factors. Thus, we also detail these known factor acetyltransferase (FAT) substrates and the demonstrated or potential roles of their acetylation in transcriptional processes.
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PMID:Acetylation of histones and transcription-related factors. 1083 22

MRG1 (melanocyte-specific gene 1 (MSG1)-related gene), a ubiquitously expressed transcription factor that interacts with p300/CBP, TATA-binding protein and Lhx2, is the founding member of a new family of transcription factors. Initial characterization of this newly discovered transcription factor has underscored its potential involvement in many important cellular processes through transcriptional modulation. We previously demonstrated that MRG1 can be induced by various biological stimuli (Sun, H. B., Zhu, Y. X., Yin, T., Sledge, G., and Yang, Y. C. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 13555-13560). As a first step in understanding its role in different biological processes, we investigated mechanisms that regulate transcription of the mouse MRG1 gene in fibroblasts. Transient transfection of Rat1 fibroblast cells with sequential 5'-deletions of mouse MRG1 promoter-luciferase fusion constructs indicated that the -104 to +121 region contains the full promoter activity. Deletion and site-directed mutations within this region revealed that the Ets-1 site at -97 to -94 and the Sp1 site at -51 to -46 are critical for MRG1 expression in fibroblasts. Gel mobility shift and supershift assays performed with Rat1 nuclear extracts identified nucleoprotein complexes binding to the Ets-1 site and the Sp1 site. In Drosophila SL2 cells, which lack the Sp and Ets family of transcription factors, expression of Sp1, Sp3, and Ets-1 or Elf-1 functionally stimulated MRG1 promoter activity in a synergistic manner. These results suggest that multiple transcription factors acting in synergy are responsible for MRG1 expression and the responsiveness of cells to different biological stimuli.
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PMID:MRG1 expression in fibroblasts is regulated by Sp1/Sp3 and an Ets transcription factor. 1111 95

The adenovirus (Ad) E1A 243R oncoprotein encodes an N-terminal transcription repression domain that is essential for early viral functions, cell immortalization, and cell transformation. The transcription repression function requires sequences within amino acids 1 to 30 and 48 to 60. To elucidate the roles of the TATA-binding protein (TBP), p300, and the CREB-binding protein (CBP) in the mechanism(s) of E1A repression, we have constructed 29 amino acid substitution mutants and 5 deletion mutants spanning the first 30 amino acids within the E1A 1-80 polypeptide backbone. These mutant E1A polypeptides were characterized with regard to six parameters: the ability to repress transcription in vitro and in vivo, to disrupt TBP-TATA box interaction, and to bind TBP, p300, and CBP. Two regions within E1A residues 1 to 30, amino acids 2 to 6 and amino acid 20, are critical for E1A transcription repression in vitro and in vivo and for the ability to interfere with TBP-TATA interaction. Replacement of 6Cys with Ala in the first region yields the most defective mutant. Replacement of 20Leu with Ala, but not substitutions in flanking residues, yields a substantially defective phenotype. Protein binding assays demonstrate that replacement of 6Cys with Ala yields a mutant completely defective in interaction with TBP, p300, and CBP. Our findings are consistent with a model in which the E1A repression function involves interaction of E1A with p300/CBP and interference with the formation of a TBP-TATA box complex.
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PMID:Adenovirus E1A N-terminal amino acid sequence requirements for repression of transcription in vitro and in vivo correlate with those required for E1A interference with TBP-TATA complex formation. 1177 19

Type I interferon (IFN) stimulates transcription through a heteromeric transcription factor that contains tyrosine-phosphorylated STAT2. We show that STAT2 recruits histone acetyltransferases (HAT) through its transactivation domain, resulting in localized transient acetylation of histones. GCN5, but not p300/CBP or PCAF, is required for STAT2 function. However, GCN5 function is impaired by the transcriptional antagonist, adenovirus E1A oncoprotein. The TFIID component TAF(II)130 potentiates STAT2 function, but TAF(II)28 or the HAT activity of TAF(II)250 do not, and transcriptional induction can proceed independently of the TATA-binding protein, TBP. Moreover, IFN-stimulated transcription was resistant to poliovirus-targeted degradation by TBP, and continued despite host-cell transcriptional shutoff during poliovirus infection. We conclude that a non-classical transcriptional mechanism combats an anticellular action of poliovirus, through a TBP-free TAF-containing complex and GCN5.
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PMID:IFN-Stimulated transcription through a TBP-free acetyltransferase complex escapes viral shutoff. 1180 63

Heterogeneous nuclear ribonucleoprotein D (hnRNP D) is implicated in transcriptional regulation. Alternative splicing of exons 2 and 7 generates four isoforms of the protein. We report here that only isoforms that contain the product of exon 2 (amino acids 79-97) were able to transactivate. Moreover, the exon 2-encoded protein domain alone was sufficient to drive transcription. TATA-binding protein and p300 interacted with a synthetic peptide corresponding to exon 2, and both proteins co-precipitated with hnRNP D. Stimulation of protein kinase A (PKA) and protein kinase C (PKC) synergistically induced the transactivating ability of hnRNP D, and the exon 2-encoded domain was sufficient for this inducibility. In kinase assays PKA phosphorylated Ser-87 of hnRNP D, whereas glycogen synthase kinase-3 beta (GSK-3 beta) phosphorylated Ser-83, but only if Ser-87 had been pre-phosphorylated by PKA. Phosphorylation of Ser-87 enhanced, whereas phosphorylation of Ser-83 repressed, transactivation. Overexpression of GSK-3 beta inhibited transactivation by hnRNP D, but stimulation of PKC negated the inhibitory effect of GSK-3 beta. We suggest that a hierarchical phosphorylation pathway regulates the transactivating ability of hnRNP D: PKA activates hnRNP D, but at the same time renders it sensitive to inhibition by GSK-3 beta; the latter inhibition can be suspended by inactivating GSK-3 beta with PKC.
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PMID:Protein kinase A enhances, whereas glycogen synthase kinase-3 beta inhibits, the activity of the exon 2-encoded transactivator domain of heterogeneous nuclear ribonucleoprotein D in a hierarchical fashion. 1190 55

Initiation of transcription of protein-encoding genes by RNA polymerase II was thought to require transcription factor TFIID, a complex comprising the TATA-binding protein (TBP) and TBP-associated factors (TAFs). In the presence of TBP-free TAF complex (TFTC), initiation of polymerase II transcription can occur in the absence of TFIID. TFTC contains several subunits that have been shown to play the role of transcriptional coactivators, including the GCN5 histone acetyltransferase (HAT), which acetylates histone H3 in a nucleosomal context. Here we analyze the coactivator function of TFTC. We show direct physical interactions between TFTC and the two distinct activation regions (H1 and H2) of the VP16 activation domain, whereas the HAT-containing coactivators, p300/CBP (CREB-binding protein), interact only with the H2 subdomain of VP16. Accordingly, cell transfection experiments demonstrate the requirement of both p300 and TFTC for maximal transcriptional activation by GAL-VP16. In agreement with this finding, we show that in vitro on a chromatinized template human TFTC mediates the transcriptional activity of the VP16 activation domain in concert with p300 and in an acetyl-CoA-dependent manner. Thus, our results suggest that these two HAT-containing co-activators, p300 and TFTC, have complementary rather than redundant roles during the transcriptional activation process.
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PMID:TATA-binding protein-free TAF-containing complex (TFTC) and p300 are both required for efficient transcriptional activation. 1210 88

The myeloid cell-specific expression and interferon-gamma (IFN-gamma) induction of Fc gamma receptor I (FcgammaRI) requires cooperation between PU.1 and signal transducer and activator of transcription 1 (Stat1) by means of mechanisms that are unknown. We found that PU.1 and Stat1 mediated distinct functions in the activation of FcgammaRI promoter. The basal activity of the natural FcgammaRI promoter was strictly dependent on PU.1, and IFN-gamma induction required both PU.1 and Stat1. Recruitment of TATA-binding protein (TBP) to the FcgammaRI promoter did not replace PU.1 in promoter activation, suggesting that TBP is not sufficient for FcgammaRI activation and that PU.1 mediates additional contacts with basal transcription machinery. In contrast, Stat1 did not interact with basal transcription machinery, but the Stat1-mediated activation of FcgammaRI promoter critically required CREB-binding protein (CBP)/p300. These results define functional cooperativity between PU.1 and Stat1 in FcgammaRI promoter activation, in which PU.1 appears to serve as a bridging factor with the basal transcription machinery and IFN-gamma-mediated induction of transcription occurs through recruitment of CBP/p300 by Stat1.
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PMID:Distinct functions for signal transducer and activator of transcription 1 and PU.1 in transcriptional activation of Fc gamma receptor I promoter. 1213 May 29


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