IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Putative role of Steroid Receptors on the modulation of PolII transcription elongation
Autor/es:
BERTUCCI, PAOLA; BALLARE, CECILIA; ALLO, MARIANO; ROCHA VIEGAS, LUCIANA; KORNBLIHTT, ALBERTO; BEATO, MIGUEL; VICENT, GUILLERMO; PECCI, ADALI
Lugar:
Iguazú
Reunión:
Simposio; Gene Expression and RNA Processing; 2011
Resumen:
It was assumed that Steroid Receptors (SRs) regulate gene expression by binding to specific Hormone Responsive Elements (HREs) located at promoters regions of target genes. Upon DNA interaction, SRs modulate pre-initiation complex formation through the recruitment of Histone covalent modifiers and ATP-dependent chromatin remodelers (ATPcr). However, genome wide analyses showed that most HREs are located far from promoters, even in intragenic regions. Additionally, ATPcr and Histone acetyltransferases, i.e GCN5 and PCAF, were found favoring PolII elongation by nucleosome displacement/disassembly or by histones acetylation. R5020, a synthetic progestin, specifically activates the Progesterone Receptor (PR) and prevents human breast epithelial tumor cells T47D from apoptosis, by enhancing the antiapoptotic isoform of human bcl-x (hbcl-x). Our aim is to characterize HREs sequences present on hbcl-x, located at 3, 45 and 60kb from the promoter, at intronic and intergenic regions. We found that kinetic of PR recruitment to these HREs is different among sites. Moreover, the closer to the 3’ of the gene they are located the higher levels of PR binding they present. PR binding pattern directly correlates with CBP and GCN5 recruitment and the concomitant to the loss of histones H2A, H3 and H4 in these HREs. Upon hormone addition, an increase in the PolII occupancy to the 3’ of the gene was observed, suggesting a hormone effect on PolII elongation efficiency. This hypothesis is supported by Proximal/Distal transcription analysis. Together, our results suggest a novel function for SRs affecting the regulation of the PolII elongation process.