CoREST represses the heat shock response mediated by HSF1.
The stress response in cells involves a rapid and transient transcriptional activation of stress genes. It has been shown that Hsp70 limits its own transcriptional activation functioning as a corepressor of heat shock factor 1 (HSF1) during the attenuation of the stress response. Here we show that the transcriptional corepressor CoREST interacts with Hsp70. Through this interaction, CoREST represses both HSF1-dependent and heat shock-dependent transcriptional activation of the hsp70 promoter. In cells expressing short hairpin RNAs directed against CoREST, Hsp70 cannot repress HSF1-dependent transcription. A reduction of CoREST levels also provoked a significant increase of Hsp70 protein levels and an increase of HSF1-dependent transactivation of hsp70 promoter. Via chromatin immunoprecipitation assays we show that CoREST is bound to the hsp70 gene promoter under basal conditions and that its binding increases during heat shock response. In conclusion, we demonstrated that CoREST is a key regulator of the heat shock stress response.
Gómez
Andrea V
AV
Millenium Nucleus in Stress and Addiction, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile.
Galleguillos
Danny
D
Maass
Juan Cristóbal
JC
Battaglioli
Elena
E
Kukuljan
Manuel
M
Andrés
María Estela
ME
D000595:Amino Acid Sequence; D002460:Cell Line; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D020868:Gene Silencing; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D009419:Nerve Tissue Proteins; C121019:RCOR1 protein, human; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014157:Transcription Factors