A Role for Gcn5-Mediated Global Histone Acetylation in Transcriptional Regulation

Abstract

Transcriptional activators often require histone acetyltransferases (HATs) for full activity. The common explanation is that activators directly recruit HATs to gene promoters to locally hyperacetylate histones and thereby facilitate transcription complex formation. However, in addition to being targeted to specific loci, HATs such as Gcn5 also modify histones genome-wide. Here we provide evidence for a role of this global HAT activity in regulated transcription. We show that activation by direct recruitment of the transcriptional machinery neither recruits Gcn5 nor induces changes in histone acetylation yet can strongly depend on Gcn5 at promoters showing a high basal state of Gcn5-mediated histone acetylation. We also show that Gcn5 dependency varies among core promoters and is influenced by the strength of interaction used to recruit the machinery and by the affinity of the latter for the core promoter. These data support a role for global Gcn5 HAT activity in modulating transcription independently of its known coactivator function.

We are most grateful to Patrick M. Schaeffer for setting up the ChIP assay. We thank Tae-Young Roh and Keji Zhao for sharing unpublished results; Walter Reith for anti-RFX1 antibodies, helpful discussions and critical reading of the manuscript; and George Thireos for discussion and support.

This work was supported by grants from the Swiss National Science Foundation (3100A0-100785) and from the EU (HPRN-CT-2000-00087, supported by OFES no. 99.0754) to M.S.