ATF1 Modulates the Heat Shock Response by Regulating the Stress-Inducible Heat Shock Factor 1 Transcription Complex

Abstract

The heat shock response is an evolutionally conserved adaptive response to high temperatures that controls proteostasis capacity and is regulated mainly by an ancient heat shock factor (HSF). However, the regulation of target genes by the stress-inducible HSF1 transcription complex has not yet been examined in detail in mammalian cells. In the present study, we demonstrated that HSF1 interacted with members of the ATF1/CREB family involved in metabolic homeostasis and recruited them on the HSP70 promoter in response to heat shock. The HSF1 transcription complex, including the chromatin-remodeling factor BRG1 and lysine acetyltransferases p300 and CREB-binding protein (CBP), was formed in a manner that was dependent on the phosphorylation of ATF1. ATF1-BRG1 promoted the establishment of an active chromatin state and HSP70 expression during heat shock, whereas ATF1-p300/CBP accelerated the shutdown of HSF1 DNA-binding activity during recovery from acute stress, possibly through the acetylation of HSF1. Furthermore, ATF1 markedly affected the resistance to heat shock. These results revealed the unanticipated complexity of the primitive heat shock response mechanism, which is connected to metabolic adaptation.

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.00754-14.

ACKNOWLEDGMENTS

We thank to Naoko Yokota for data analysis of the ChIP-seq.

This work was supported in part by grants from the Japan Society for the Promotion of Science (R.T., M.F., E.T., N.H., and A.N.), a Grant-in-Aid for Scientific Research on Innovative Areas (Cross Talk between Transcriptional Control and Energy Pathways, Mediated by Hub Metabolites) (A.N.), Takeda Science Foundation Special Project Research (A.N.), the Uehara Science Foundation (M.F.), and the Yamaguchi University Research Project on STRESS (A.N.).