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Mol. Cell. Biol. doi:10.1128/MCB.01798-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Isw2 chromatin remodeling ATPase cooperates with the Fkh2 transcription factor to represses transcription of the B-type cyclin CLB2

Division of Molecular Genetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK

^* To whom correspondence should be addressed. Email: jane.mellor{at}bioch.ox.ac.uk.

	Abstract

Fork head (Fkh) transcription factors influence cell death, proliferation, differentiation and the cell cycle. In yeast, Fkh2 both activates and represses transcription of CLB2 encoding a B-type cyclin. CLB2 is expressed during G₂/M and repressed during G₁. Fkh2 recruits the co-activator Ndd1, an interaction which is promoted by Clb2/Cdk1-dependent phosphorylation of Ndd1 suggesting that CLB2 is auto-regulated. Ndd1 is proposed to function by antagonizing Fkh2-mediated repression but nothing is known about the mechanism. Here we ask how Fkh2 represses CLB2. We show that Fkh2 controls a repressive chromatin structure that initiates in the early coding region of CLB2 and spreads up the promoter during M and G₁. The Isw2 chromatin remodeling ATPase cooperates with Fkh2 to remodel the chromatin and repress CLB2 expression throughout the cell cycle. In addition, the related factors Isw1 and Fkh1 configure the chromatin at the early coding region and negatively regulate CLB2 expression but only during G₂/M. Thus the cooperative actions of two fork head transcription factors and two chromatin remodeling ATPases combine to regulate CLB2. We propose that chromatin mediated repression by Isw1 and Isw2 may serve to limit activation of CLB2 expression by the Clb2/Cdk1 kinase during G₂/M and to fully repress expression during G₁.

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