Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.99.3 (PRE)
 1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progesterone receptor (PR) functions as a transcription factor that modulates the transcription of target genes in response to progesterone and other signals. The transcriptional activity of PR requires the involvement of coactivators such as steroid receptor coactivator-1 (SRC-1). To dissect the role of SRC-1 in PR transactivation, we established an in vitro transcription system with chromatin templates, in which PR induced transcription in a ligand-dependent and PRE-dependent manner. In the presence of ligand, purified PR bound to chromatin templates, resulting in chromatin remodeling. With this system, the ability of purified SRC-1 to act as a coactivator of PR was examined. SRC-1 potentiated transcription by ligand-activated PR, whereas it had no effect on transcription in the absence of ligands. As SRC-1 possesses intrinsic histone acetyltransferase activity, we tested the role of acetylation in PR-mediated transcription by using a histone deacetylase inhibitor, trichostatin A (TSA). We found that addition of TSA strongly enhanced PR-dependent transcription on chromatin but not on naked DNA template, and the effects of SRC-1 and TSA on PR transactivation were partially redundant. In addition, SRC-1 was able to potentiate PR transactivation with nonchromatin templates. Thus, our results substantiate a two-step mechanism whereby recruitment of coactivator SRC-1 by the ligand-activated PR in vivo leads to (i) chromatin remodeling through histone acetylation and (ii) recruitment/stabilization of the preinitiation complex.
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PMID:Steroid receptor coactivator-1 (SRC-1) enhances ligand-dependent and receptor-dependent cell-free transcription of chromatin. 1044 19

Poly(dA.dT) sequences (T-tracts) are abundant genomic DNA elements with unusual properties in vitro and an established role in transcriptional regulation of yeast genes. In vitro T-tracts are rigid, contribute to DNA bending, affect assembly in nucleosomes and generate a characteristic pattern of CPDs (cyclobutane pyrimidine dimers) upon irradiation with UV light (UV photofootprint). In eukaryotic cells, where DNA is packaged in chromatin, the DNA structure of T-tracts is unknown. Here we have used in vivo UV photofootprinting and DNA repair by photolyase to investigate the structure and accessibility of T-tracts in yeast promoters (HIS3, URA3 and ILV1). The same characteristic photofootprints were obtained in yeast and in naked DNA, demonstrating that the unusual T-tract structure exists in living cells. Rapid repair of CPDs in the T-tracts demonstrates that these T-tracts were not folded in nucleosomes. Moreover, neither datin, a T-tract binding protein, nor Gcn5p, a histone acetyltransferase involved in nucleosome remodelling, showed an influence on the structure and accessibility of T-tracts. The data support a contribution of this unusual DNA structure to transcriptional regulation.
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PMID:Poly(dA.dT) sequences exist as rigid DNA structures in nucleosome-free yeast promoters in vivo. 1105 3