Putative role of steroid receptors on the modulation of POLII transcription elongation

BERTUCCI, P.Y.; BALLARE, C; ALLÓ, M; ROCHA VIEGAS, L; NACHT, AS; KORNBLIHTT, A.R.; BEATO, M.; VICENT, G.P.; PECCI, A.

Catarates del Iguazú

Simposio; Symposium on Gene Expression and RNA processing; 2011

ICGEB

It was assumed that Steroid Receptors (SRs) regulate gene expression through Hormone Responsive Elements (HREs) located at promoter regions of target genes. Upon DNA interaction, SRs modulate pre-initiation complex formation by recruiting 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 (HATs), i.e GCN5 and PCAF, were found favoring Pol II elongation by nucleosome displacement/disassembly or by histone acetylation. Activation of the Progesterone Receptor (PR) by progestins prevents human breast epithelial tumor cells T47D from apoptosis, by increasing the antiapoptotic isoform of human bcl-x gene transcription. Our aim is to characterize the HREs sequences present in bcl-x, located at 3, 45 and 60kb away from the promoters, at intronic and intergenic regions. We found that kinetic of PR recruitment to these HREs is different among sites. Moreover, a positive correlation between the locations of the HREs from the 5´ to the3´of the gene and the strength of PR binding were also found. After hormone addition PR is recruited along with the HATs CBP and GCN5 and a concomitant depletion of histones H2A, H3 and H4 was observed. These changes are associated with an increase in the Pol II occupancy at the 3’ of the gene, suggesting a hormonal effect on Pol II elongation efficiency. This hypothesis is supported by Proximal/Distal transcription analysis. Thus, our results suggest a novel function for SRs affecting the regulation of the Pol II elongation process.