Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation.

BERTUCCI, P.Y.; NACHT, AS; ALLÓ, M; ROCHA VIEGAS, LUCIANA; BALLARE, C; SORONELLAS, DANIEL; CASTELLANOS, G; ZAURIN, ROSER; KORNBLIHTT, A.E.; BEATO, M; VICENT, G.P.; PECCI, A.

NUCLEIC ACIDS RESEARCH

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2013 vol. 41 p. 6072 - 6086

0305-1048

Steroid receptors were classically described 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 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 specifically in the proximity of the intragenic PRbs. PR also mediated the recruitment of the positive elongation factor pTEFb, favoring RNA polymerase II (Pol II) in its active elongating form. 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.