Phosphorylation and Recruitment of BAF60c in Chromatin Remodeling for Lipogenesis in Response to Insulin

Mol Cell. 2013 Jan 24;49(2):283-97. doi: 10.1016/j.molcel.2012.10.028. Epub 2012 Dec 6.

Abstract

Fatty acid and triglyceride synthesis is induced in response to feeding and insulin. This lipogenic induction involves coordinate transcriptional activation of lipogenic enzymes, including fatty acid synthase and glycerol-3-phosphate acyltransferase. We recently reported the importance of USF-1 phosphorylation and subsequent acetylation in insulin-induced lipogenic gene activation. Here, we show that Brg1/Brm-associated factor (BAF) 60c is a specific chromatin remodeling component for lipogenic gene transcription in liver. In response to insulin, BAF60c is phosphorylated at S247 by atypical PKCζ/λ, which causes translocation of BAF60c to the nucleus and allows a direct interaction of BAF60c with USF-1 that is phosphorylated by DNA-PK and acetylated by P/CAF. Thus, BAF60c is recruited to form the lipoBAF complex to remodel chromatin structure and to activate lipogenic genes. Consequently, BAF60c promotes lipogenesis in vivo and increases triglyceride levels, demonstrating its role in metabolic adaption to activate the lipogenic program in response to feeding and insulin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • Chromatin Assembly and Disassembly*
  • Energy Metabolism
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism
  • Hep G2 Cells
  • Humans
  • Insulin / physiology*
  • Lipogenesis*
  • Mice
  • Mice, SCID
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Kinase C / metabolism
  • Protein Processing, Post-Translational*
  • Protein Subunits / metabolism
  • Protein Transport
  • Signal Transduction
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Upstream Stimulatory Factors / metabolism

Substances

  • Insulin
  • Protein Subunits
  • SMARCD3 protein, human
  • Transcription Factors
  • USF1 protein, human
  • Upstream Stimulatory Factors
  • Fatty Acid Synthases
  • Protein Kinase C