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Molecular and Cellular Biology, April 2007, p. 2848-2860, Vol. 27, No. 8
0270-7306/07/$08.00+0     doi:10.1128/MCB.01798-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Isw2 Chromatin-Remodeling ATPase Cooperates with the Fkh2 Transcription Factor To Repress Transcription of the B-Type Cyclin Gene CLB2{triangledown}

Julia A. Sherriff, Nicholas A. Kent, and Jane Mellor*

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

Received 22 September 2006/ Returned for modification 24 October 2006/ Accepted 24 January 2007

Forkhead (Fkh) transcription factors influence cell death, proliferation, and differentiation and the cell cycle. In Saccharomyces cerevisiae, Fkh2 both activates and represses transcription of CLB2, encoding a B-type cyclin. CLB2 is expressed during G2/M phase and repressed during G1. Fkh2 recruits the coactivator Ndd1, an interaction which is promoted by Clb2/Cdk1-dependent phosphorylation of Ndd1, suggesting that CLB2 is autoregulated. 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 the M and G1 phases. 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 phase. Thus, the cooperative actions of two forkhead 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.


* Corresponding author. Mailing address: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom. Phone: 44 1 865 275303. Fax: 44 1 865 275297. E-mail: jane.mellor{at}bioch.ox.ac.uk

{triangledown} Published ahead of print on 5 February 2007.


Molecular and Cellular Biology, April 2007, p. 2848-2860, Vol. 27, No. 8
0270-7306/07/$08.00+0     doi:10.1128/MCB.01798-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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