Histone Acetylation at Promoters Is Differentially Affected by Specific Activators and Repressors

Abstract

We analyzed the relationship between histone acetylation and transcriptional regulation at 40 Saccharomyces cerevisiaepromoters 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.

ACKNOWLEDGMENTS

We thank Laurent Kuras for cross-linked chromatin samples and advice on chromatin immunoprecipitation, Laurie Stargell for TBP antibodies, and Juliet Reid and Elmar vom Baur for discussing unpublished observations on histone acetylation.

This work was supported by grants to K.S. from the National Institutes of Health (GM30186 and GM53720).

ADDENDUM IN PROOF

Since the submission of this paper, J. Wu et al. (Mol. Cell7:117–126, 2001) showed that Tup1 repression is associated with deacetylation of histones H3 and H2B and that Tup1 interacts in vitro with an isolated subunit of the HDAI histone deacetylase complex.