Article
- The EMBO Journal (2004) 23, 1348 - 1359
- doi:10.1038/sj.emboj.7600143
Published online: 4 March 2004
Subject Category:
Tandem bromodomains in the chromatin remodeler RSC recognize acetylated histone H3 Lys14
Margaret Kasten1, Heather Szerlong1, Hediye Erdjument-Bromage2, Paul Tempst2, Michel Werner3 and Bradley R Cairns1
- Howard Hughes Medical Institute and Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA
- Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
- Service de Biochimie et Génétique Moleculaire, Bâtiment 44, CEA/Saclay, Gif-Sir-Yvette, France
Correspondence to:
Bradley R Cairns, Howard Hughes Medical Institute and Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Room 4362, 2000 Circle of Hope, Salt Lake City, UT 84112, USA. Tel.: +1 801 585 1822; Fax: +1 801 585 6410; E-mail: brad.cairns@hci.utah.edu
Received 28 August 2003; Accepted 3 February 2004
Abstract
The coordination of chromatin remodeling with chromatin modification is a central topic in gene regulation. The yeast chromatin remodeling complex RSC bears multiple bromodomains, motifs for acetyl-lysine and histone tail interaction. Here, we identify and characterize Rsc4 and show that it bears tandem essential bromodomains. Conditional rsc4 bromodomain mutations were isolated, and were lethal in combination with gcn5
, whereas combinations with esa1 grew well. Replacements involving Lys14 of histone H3 (the main target of Gcn5), but not other H3 or H4 lysine residues, also conferred severe growth defects to rsc4 mutant strains. Importantly, wild-type Rsc4 bound an H3 tail peptide acetylated at Lys14, whereas a bromodomain mutant derivative did not. Loss of particular histone deacetylases suppressed rsc4 bromodomain mutations, suggesting that Rsc4 promotes gene activation. Furthermore, rsc4 mutants displayed defects in the activation of genes involved in nicotinic acid biosynthesis, cell wall integrity, and other pathways. Taken together, Rsc4 bears essential tandem bromodomains that rely on H3 Lys14 acetylation to assist RSC complex for gene activation.
Keywords:
- bromodomain,
- chromatin remodeling,
- histone acetylation,
- RSC
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