Bromodomain factors of BET family are new essential actors of pericentric heterochromatin transcriptional activation in response to heat shock

Neda Hoghoughi,Solenne Dufour,André Verdel,Sylvain Daujat,Claire Vourc’H,Robert Schneider,Edwige Col,Eric Folco,Sivan Koskas,Jessica Penin,Hector Hernandez-Vargash,Nicolas Reynoird,Cécile Caron,Virginie Faure,Maria Ouzounova,Zdenko Herceg,Marc Vigneron,Saadi Khochbin

doi:10.1038/s41598-017-05343-8

Abstract

The heat shock response is characterized by the transcriptional activation of both hsp genes and noncoding and repeated satellite III DNA sequences located at pericentric heterochromatin. Both events are under the control of Heat Shock Factor I (HSF1). Here we show that under heat shock, HSF1 recruits major cellular acetyltransferases, GCN5, TIP60 and p300 to pericentric heterochromatin leading to a targeted hyperacetylation of pericentric chromatin. Redistribution of histone acetylation toward pericentric region in turn directs the recruitment of Bromodomain and Extra-Terminal (BET) proteins BRD2, BRD3, BRD4, which are required for satellite III transcription by RNAP II. Altogether we uncover here a critical role for HSF1 in stressed cells relying on the restricted use of histone acetylation signaling over pericentric heterochromatin (HC).

Highlights

To cite this version: Edwige Col, Neda Hoghoughi, Solenne Dufour, Jessica Penin, Sivan Koskas, et al
Coimmunoprecipitation of p300/ CREB-binding protein (CBP) with Heat Shock Factor 1 (HSF1) has already been reported[22, 29] and the enrichment of CBP at nSBs2 described. We extend here these findings to two other essential transcriptional co-activators belonging to two additional Histone Acetyl Transferases (HATs) families: GCN5, and TIP60 and have identified the domains possibly involved in their interaction with HSF1
It reinforces the possibility that a massive recruitment of HATs at nSBs may deplete them from the rest of the nucleus and participate to the global down regulation of gene expression occuring in heat-shocked cells[23]

Summary

Introduction

To cite this version: Edwige Col, Neda Hoghoughi, Solenne Dufour, Jessica Penin, Sivan Koskas, et al. We provide new evidence that unlike hsp[70] gene, JQ1 inhibits sat III transcription by RNA polymerase II (RNAP II), pointing to the existence of important differences in the mechanisms of activation of two major targets of the heat shock response.

Results

Conclusion