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)

Infected-cell polypeptide 4 (ICP4) of herpes simplex virus is both a transcriptional activator and a repressor. It has been previously demonstrated that both SP1-activated transcription and USF-activated transcription are repressed by ICP4 without affecting basal transcription (B. Gu, R. Rivera-Gonzalez, C. A. Smith, and N. A. DeLuca, Proc. Natl. Acad. Sci. USA 90:9528-9532, 1993; R. Rivera-Gonzalez, A. N. Imbalzano, B. Gu, and N.A. DeLuca, Virology 202:550-564, 1994). In this study, it was found that ICP4 repressed the activation function of two other activators, VP16 and ICP4 itself, in vitro. ICP4 inhibited transcription by interfering with the formation of transcription initiation complexes without affecting transcription elongation. Repression of activator function required that an ICP4 DNA binding site was present in one orientation within approximately 45 bp 3' to the TATA box. DNA binding by ICP4 was necessary but not sufficient for repression. ICP4 has been shown to form tripartite complexes cooperatively with the TATA box-binding protein and TFIIB on DNA containing an ICP4 binding site and a TATA box (C. A. Smith, P. Bates, R. Rivera-Gonzalez, B. Gu, and N. DeLuca, J. Virol. 67:4676-4687, 1993). A region of ICP4 that enables the molecule to form tripartite complexes was also required in addition to the DNA binding domain for efficient repression. Moreover, repression was observed only when the ICP4 binding site was in a position that resulted in the formation of tripartite complexes. Together, the data suggest that ICP4 represses transcription by binding to DNA in a precise way so that it may interact with the basal transcription complex and inhibit some general step involved in the function of activators. The steps or interactions involved in transcriptional activation that are inhibited by ICP4 are discussed.
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PMID:Repression of activator-mediated transcription by herpes simplex virus ICP4 via a mechanism involving interactions with the basal transcription factors TATA-binding protein and TFIIB. 779 69

T cell development within the thymus involves the ordered expression of a number of tissue-specific components such as the CD2 gene. Control of expression of this gene is regulated by a well characterized 3' enhancer together with a promoter and upstream elements. The CD2 promoter is typical of a group of T cell-specific promoters that lack a TATA box and use multiple sites for initiation of transcription. An "E box" motif CACGTG, located just upstream from the most 5' initiation start site, was found to contribute a major effect to the level of basal transcription of a reporter gene. Analysis of the proteins in T cell extracts that bound to this site revealed that the bHLH-LZ protein USF was the major component. A functional role for USF was established in transient transfection experiments. Thus, this protein restored full promoter activity following repression caused by cotransfection with the E box binding bHLH-LZ protein Max. Taken together, these results indicate that an E box motif is critical to expression of the CD2 gene during T cell development and that the HLH protein USF acts as a transcriptional activator of the CD2 promoter.
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PMID:The helix-loop-helix containing transcription factor USF activates the promoter of the CD2 gene. 792 76

The microE3 E box within the immunoglobulin heavy-chain (IgH) enhancer binds several proteins of the basic helix-loop-helix-leucine zipper (bHLHzip) class, including TFE3, USF1, and Max. Both TFE3 and USF have been described as transcriptional activators, and so we investigated their possible roles in activating the IgH enhancer in vivo. Although TFE3 activated various enhancer-based reporters, both USF1 and Max effectively inhibited transcription. Inhibition by USF correlated with the lack of a strong activation domain and was the result of the protein neutralizing the microE3 site. The effects of dominant-negative derivatives of TFE3 and USF1 confirmed that TFE3, or a TFE3-like protein, is the primary cellular bHLHzip protein that activates the IgH enhancer. In addition to providing a physiological role for TFE3, our results call into question the traditional view of USF1 as an obligate transcriptional activator.
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PMID:Selective utilization of basic helix-loop-helix-leucine zipper proteins at the immunoglobulin heavy-chain enhancer. 897 81

The GATA-3 transcription factor is required for development of the T-cell lineage and Th2 cytokine gene expression in CD4 T-cells. We have mapped the DNase-I-hypersensitive (HS) regions of the human GATA-3 gene in T-cells and non-T-cells and studied their transcriptional activities. HS I-III, located 5' from the transcriptional initiation site, were found in hematopoietic and non-hematopoietic cells, whereas HS IV-VII, located 3' from the transcriptional start site, were exclusively observed in T-cells. Among these hypersensitive sites, two transcriptional control elements were found, one in the first intron of the GATA-3 gene and the other between 8.3 and 5.9 kilobases 5' from the GATA-3 transcriptional initiation site. The first intron acted as a strong transcriptional activator in a position-dependent manner and with no cell-type specificity. The upstream regulatory element could confer T-cell specificity to the GATA-3 promoter activity, and analysis of this region revealed a 707-base pair silencer that drastically inhibited GATA-3 promoter activity in non-T-cells. Two CAGGTG E-boxes, located at the 5'- and 3'-ends of the silencer, were necessary for this silencer activity. The 3'-CAGGTG E-box could bind USF proteins, the ubiquitous repressor ZEB, or the basic helix-loop-helix proteins E2A and HEB, and we showed that a competition between ZEB and E2A/HEB proteins is involved in the silencer activity.
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PMID:T-cell expression of the human GATA-3 gene is regulated by a non-lineage-specific silencer. 1003 51

During adipocyte differentiation, CCAAT/enhancer-binding protein alpha (C/EBPalpha) functions as a pleiotropic transcriptional activator of numerous adipocyte genes. The promoter of the C/EBPalpha gene has an E-box upstream of C/EBP binding site. Deletion or mutation of the E-box decreases promoter activity, suggesting that the E-box participates in the regulation of C/EBPalpha expression. Protein binding to the E-box during the adipocyte differentiation is increased as indicated by EMSA and UV cross-linking. Purification of the E-box binding proteins from differentiated 3T3-L1 adipocytes, showed that USF and AP-4 are associated with the E-box. Supershift analysis showed that USF1 and USF2 bind to this element as heterodimers, whereas the addition of anti-AP-4 antibody enhanced the binding complex, suggesting that AP-4 negatively regulates the promoter activity. The expression of AP-4 is reciprocally regulated with USF-1 during adipocyte differentiation. These findings suggest that USF-1 and 2 play roles in C/EBPalpha expression, whereas the AP-4 represses it.
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PMID:Upstream stimulatory factors regulate the C/EBP alpha gene during differentiation of 3T3-L1 preadipocytes. 1723 50