Distinct stimulus-specific histone modifications at hsp70 chromatin targeted by the transcription factor heat shock factor-1.
A question of major current interest is whether histone modification at a given gene correlates simply with transcriptional status or if distinctive modifications appear depending on how that gene is activated. The stress-inducible gene Hsp70 is activated by heat shock or by sodium arsenite. Heat shock produces acetylation of histone H4 at Hsp70 chromatin, whereas arsenite produces both H4 acetylation and H3 phosphorylation at the gene. Histone H3 remains markedly hypoacetylated at Hsp70 under these conditions. Arsenite, but not heat shock, requires signaling via p38 MAP kinase for Hsp70 induction and histone H3 phosphorylation. However, independently of p38 MAP kinase, both stresses strongly activate the transcription factor Hsf1. Using Hsf1-/- cells, we show that this factor is responsible for targeting histone H4 acetylation to Hsp70 chromatin. We establish here that histone modifications at inducible genes are not simply a reflection of transcriptional activity, but are strictly dependent on the stimulus used for induction.
Nuclear Signalling Laboratory, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
Stuart
S
Thomson
Angela
A
Hollis
Catherine A
CA
Hazzalin
Louis C
LC
Mahadevan
D000818:Animals; D018053:Arsenites / Q000378:metabolism; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006657:Histones / Q000378:metabolism*; D006358:Hot Temperature; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017670:Sodium Compounds / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D018053:Arsenites; D002843:Chromatin; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006657:Histones; C490017:Hsf1 protein, mouse; D017670:Sodium Compounds; D014157:Transcription Factors; C017947:sodium arsenite; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases