Chromatin remodeling complex interacts with ADD1/SREBP1c to mediate insulin-dependent regulation of gene expression

Mol Cell Biol. 2007 Jan;27(2):438-52. doi: 10.1128/MCB.00490-06. Epub 2006 Oct 30.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Animals
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Gene Expression Regulation
  • Insulin / pharmacology
  • Insulin / physiology*
  • Male
  • Mice
  • Mice, Transgenic
  • Promoter Regions, Genetic
  • Sterol Regulatory Element Binding Protein 1 / metabolism*
  • Transcription Factors / metabolism

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Insulin
  • Smarcc1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors