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Molecular and Cellular Biology, April 2001, p. 2802-2814, Vol. 21, No. 8
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.8.2802-2814.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Temporal Recruitment of the mSin3A-Histone Deacetylase Corepressor Complex to the ETS Domain Transcription Factor Elk-1

Shen-Hsi Yang,1,2 Elaine Vickers,1,2 Alexander Brehm,3,dagger Tony Kouzarides,3 and Andrew D. Sharrocks1,2,*

School of Biological Sciences, University of Manchester, Manchester M13 9PT,1 School of Biochemistry and Genetics, The Medical School, University of Newcastle Upon Tyne, Newcastle Upon Tyne NE2 4HH,2 and Wellcome/CRC Institute, Cambridge CB2 1QR,3 United Kingdom

Received 13 September 2000/Returned for modification 25 October 2000/Accepted 25 January 2001

The transcriptional status of eukaryotic genes is determined by a balance between activation and repression mechanisms. The nuclear hormone receptors represent classical examples of transcription factors that can regulate this balance by recruiting corepressor and coactivator complexes in a ligand-dependent manner. Here, we demonstrate that the equilibrium between activation and repression via a single transcription factor, Elk-1, is altered following activation of the Erk mitogen-activated protein kinase cascade. In addition to its C-terminal transcriptional activation domain, Elk-1 contains an N-terminal transcriptional repression domain that can recruit the mSin3A-histone deacetylase 1 corepressor complex. Recruitment of this corepressor is enhanced in response to activation of the Erk pathway in vivo, and this recruitment correlates kinetically with the shutoff of one of its target promoters, c-fos. Elk-1 therefore undergoes temporal activator-repressor switching and contributes to both the activation and repression of target genes following growth factor stimulation.

* Corresponding author. Mailing address: School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Rd., Manchester M13 9PT, United Kingdom. Phone: 0044-161 275 5979. Fax: 0044-161 275 5082. E-mail: a.d.sharrocks{at}man.ac.uk.

dagger Present address: Molekularbiologie, Adolf-Butenandt-Institut, 80336 Munich, Germany.

Molecular and Cellular Biology, April 2001, p. 2802-2814, Vol. 21, No. 8
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.8.2802-2814.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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