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Molecular and Cellular Biology, June 2008, p. 3894-3904, Vol. 28, No. 12
0270-7306/08/$08.00+0     doi:10.1128/MCB.00322-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

CHD8 Is an ATP-Dependent Chromatin Remodeling Factor That Regulates β-Catenin Target Genes{triangledown}

Brandi A. Thompson, Véronique Tremblay, Grace Lin, and Daniel A. Bochar*

Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109

Received 26 February 2008/ Accepted 22 March 2008

ATP-dependent chromatin remodeling by the CHD family of proteins plays an important role in the regulation of gene transcription. Here we report that full-length CHD8 interacts directly with β-catenin and that CHD8 is also recruited specifically to the promoter regions of several β-catenin-responsive genes. Our results indicate that CHD8 negatively regulates β-catenin-targeted gene expression, since short hairpin RNA against CHD8 results in the activation of several β-catenin target genes. This regulation is also conserved through evolution; RNA interference against kismet, the apparent Drosophila ortholog of CHD8, results in a similar activation of β-catenin target genes. We also report the first demonstration of chromatin remodeling activity for a member of the CHD6-9 family of proteins, suggesting that CHD8 functions in transcription through the ATP-dependent modulation of chromatin structure.


* Corresponding author. Mailing address: The University of Michigan Medical School, 3301E MSRB III, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-0606. Phone: (734) 647-3734. Fax: (734) 763-7799. E-mail: dbochar{at}umich.edu

{triangledown} Published ahead of print on 31 March 2008.


Molecular and Cellular Biology, June 2008, p. 3894-3904, Vol. 28, No. 12
0270-7306/08/$08.00+0     doi:10.1128/MCB.00322-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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