title: Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation.
abstract: Steroid receptors were classically described for regulating transcription by binding to target gene promoters. However, genome-wide studies reveal that steroid receptors-binding sites are mainly located at intragenic regions. To determine the role of these sites, we examined the effect of progestins on the transcription of the bcl-x gene, where only intragenic progesterone receptor-binding sites (PRbs) were identified. We found that in response to hormone treatment, the PR is recruited to these sites along with two histone acetyltransferases CREB-binding protein (CBP) and GCN5, leading to an increase in histone H3 and H4 acetylation and to the binding of the SWI/SNF complex. Concomitant, a more relaxed chromatin was detected along bcl-x gene mainly in the regions surrounding the intragenic PRbs. PR also mediated the recruitment of the positive elongation factor pTEFb, favoring RNA polymerase II (Pol II) elongation activity. Together these events promoted the re-distribution of the active Pol II toward the 3'-end of the gene and a decrease in the ratio between proximal and distal transcription. These results suggest a novel mechanism by which PR regulates gene expression by facilitating the proper passage of the polymerase along hormone-dependent genes.
authors: IFIBYNE-CONICET, Buenos Aires C1428EGA, Argentina.
authors: Paola Y
authors: PY
authors: Bertucci
authors: A Silvina
authors: AS
authors: Nacht
authors: Mariano
authors: M
authors: Alló
authors: Luciana
authors: L
authors: Rocha-Viegas
authors: Cecilia
authors: C
authors: Ballaré
authors: Daniel
authors: D
authors: Soronellas
authors: Giancarlo
authors: G
authors: Castellano
authors: Roser
authors: R
authors: Zaurin
authors: Alberto R
authors: AR
authors: Kornblihtt
authors: Miguel
authors: M
authors: Beato
authors: Guillermo P
authors: GP
authors: Vicent
authors: Adali
authors: A
authors: Pecci
mesh_terms: D017398:Alternative Splicing; D001665:Binding Sites; D050882:CREB-Binding Protein / Q000378:metabolism; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry; D006801:Humans; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D011397:Promegestone / Q000494:pharmacology; D012319:RNA Polymerase II / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D061805:Transcription Elongation, Genetic; D051020:bcl-X Protein / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D050882:CREB-Binding Protein; D002843:Chromatin; D042925:Positive Transcriptional Elongation Factor B; D011397:Promegestone; D012319:RNA Polymerase II; D011980:Receptors, Progesterone; D051020:bcl-X Protein; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C494363:CREBBP protein, human
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