Bertucci, Paola Y.Nacht, A. SilvinaAlló, MarianoRocha-Viegas, LucianaBallaré, Cecilia JuliaSoronellas, DanielCastellano, GiancarloZaurín Quer, RoserKornblihtt, Alberto R.Beato, MiguelVicent, Guillermo PabloPecci, Adali2023-11-202023-11-202013Bertucci PY, Nacht AS, Alló M, Rocha-Viegas L, Ballaré C, Soronellas D, et al. Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation. Nucleic Acids Research. 2013 Jul 1;41(12):6072-86. DOI: 10.1093/nar/gkt3270305-1048http://hdl.handle.net/10230/58299Steroid 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.application/pdfeng© The Author(s) 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.comProgesterona -- ReceptorsEsteroidesHormones esteroidesinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1093/nar/gkt327info:eu-repo/semantics/openAccess