Artículos de revistas
Progesterone Receptor induces bcl-x expression through intragenic binding sites favoring RNA Polymerase II elongation
Fecha
2013-05-02Registro en:
Bertucci, Paola Yanina; Nacht, Ana Silvina; Alló, Mariano; Rocha Viegas, Luciana; Ballaré, Cecilia; et al.; Progesterone Receptor induces bcl-x expression through intragenic binding sites favoring RNA Polymerase II elongation; Oxford University Press; Nucleic Acids Research; 41; 12; 2-5-2013; 6072-6086
0305-1048
1362-4962
Autor
Bertucci, Paola Yanina
Nacht, Ana Silvina
Alló, Mariano
Rocha Viegas, Luciana
Ballaré, Cecilia
Soronellas, Daniel
Castellano, Giancarlo
Zaurin, Roser
Kornblihtt, Alberto Rodolfo
Beato, Miguel
Vicent, Guillermo
Pecci, Adali
Resumen
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 pro- gestins 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 sur- rounding 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-dis- tribution of the active Pol II toward the 30-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 ex- pression by facilitating the proper passage of the polymerase along hormone-dependent genes.