Histone acetylation at promoters is differentially affected by specific activators and repressors.
We analyzed the relationship between histone acetylation and transcriptional regulation at 40 Saccharomyces cerevisiae promoters that respond to specific activators and repressors. In accord with the general correlation between histone acetylation and transcriptional activity, Gcn4 and the general stress activators (Msn2 and Msn4) cause increased acetylation of histones H3 and H4. Surprisingly, Gal4-dependent activation is associated with a dramatic decrease in histone H4 acetylation, whereas acetylation of histone H3 is unaffected. A specific decrease in H4 acetylation is also observed, to a lesser extent, at promoters activated by Hap4, Adr1, Met4, and Ace1. Activation by heat shock factor has multiple effects; H4 acetylation increases at some promoters, whereas other promoters show an apparent decrease in H3 and H4 acetylation that probably reflects nucleosome loss or gross alteration of chromatin structure. Repression by targeted recruitment of the Sin3-Rpd3 histone deacetylase is associated with decreased H3 and H4 acetylation, whereas repression by Cyc8-Tup1 is associated with decreased H3 acetylation but variable effects on H4 acetylation; this suggests that Cyc8-Tup1 uses multiple mechanisms to reduce histone acetylation at promoters. Thus, individual activators confer distinct patterns of histone acetylation on target promoters, and transcriptional activation is not necessarily associated with increased acetylation. We speculate that the activator-specific decrease in histone H4 acetylation is due to blocking the access or function of an H4-specific histone acetylase such as Esa1.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
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Deckert
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Struhl
D000107:Acetylation; D050976:Basic-Leucine Zipper Transcription Factors; D023081:CCAAT-Binding Factor / Q000378:metabolism; D003300:Copper / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D005800:Genes, Fungal; D018869:Heat-Shock Response; D006655:Histone Deacetylases; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
C074682:ADR1 protein, S cerevisiae; D050976:Basic-Leucine Zipper Transcription Factors; D023081:CCAAT-Binding Factor; C060256:CUP2 protein, S cerevisiae; C065455:CYC8 protein, S cerevisiae; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C061437:HAP4 protein, S cerevisiae; D006657:Histones; C073675:MET4 protein, S cerevisiae; D009687:Nuclear Proteins; D012097:Repressor Proteins; C071731:SIN3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C066502:TUP1 protein, S cerevisiae; D015534:Trans-Activators; D014157:Transcription Factors; C103264:ZAP1 protein, S cerevisiae; D003300:Copper; D011494:Protein Kinases; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases