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Molecular and Cellular Biology, January 2007, p. 438-452, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.00490-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Chromatin Remodeling Complex Interacts with ADD1/SREBP1c To Mediate Insulin-Dependent Regulation of Gene Expression{triangledown}

Yun Sok Lee,1,2 Dong Hyun Sohn,1,2,3 Daehee Han,1,2,3 Han-Woong Lee,4,{dagger} Rho Hyun Seong,1,2,3 and Jae Bum Kim1,2*

Department of Biological Sciences, Seoul National University, Seoul 151-742, South Korea,1 Research Center for Functional Cellulomics, Seoul National University, Seoul 151-742, South Korea,2 Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, South Korea,3 Sung Kyun Kwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, South Korea4

Received 21 March 2006/ Returned for modification 9 May 2006/ Accepted 20 October 2006

Insulin plays a critical role in whole-body energy homeostasis by regulating lipid and glucose metabolism. In fat and liver tissues, ADD1/SREBP1c is a key transcription factor to mediate insulin-dependent regulation of gene expression. Although transcriptional and proteolytic activation of ADD1/SREBP1c has been studied intensively, the mechanism by which insulin regulates expression of its target genes with ADD1/SREBP1c at the chromatin level is unclear. Here, we reveal that SWI/SNF chromatin remodeling factors interact with the ADD1/SREBP1c and actively regulate insulin-dependent gene expression. Insulin enhanced recruitment of SWI/SNF chromatin remodeling factors to its target gene promoters with concomitant changes in the chromatin structures as well as gene expression. Furthermore, in vivo overexpression of BAF155/SRG3, a component of the SWI/SNF complex, substantially promoted insulin target gene expression and insulin sensitivity. Taken together, our results suggest that the SWI/SNF chromatin remodeling complexes confer not only insulin-dependent gene expression but also insulin sensitivity in vivo via interaction with ADD1/SREBP1c.

* Corresponding author. Mailing address: Department of Biological Sciences, Seoul National University, San 56-1, Sillim-Dong, Kwanak-Gu, Seoul 151-742, South Korea. Phone: 82 2 880 5852. Fax: 82 2 878 5852. E-mail: jaebkim{at}snu.ac.kr.

{triangledown} Published ahead of print on 30 October 2006.

{dagger} Present address: Department of Biochemistry, Yonsei University, Seoul 120-749, South Korea.

Molecular and Cellular Biology, January 2007, p. 438-452, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.00490-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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