Interferon Regulatory Factors Are Transcriptional Regulators of Adipogenesis

Cell Metab. 2008 Jan;7(1):86-94. doi: 10.1016/j.cmet.2007.11.002.

Abstract

We have sought to identify transcriptional pathways in adipogenesis using an integrated experimental and computational approach. Here, we employ high-throughput DNase hypersensitivity analysis to find regions of altered chromatin structure surrounding key adipocyte genes. Regions that display differentiation-dependent changes in hypersensitivity were used to predict binding sites for proteins involved in adipogenesis. A high-scoring example was a binding motif for interferon regulatory factor (IRF) family members. Expression of all nine mammalian IRF mRNAs is regulated during adipogenesis, and several bind to the identified motifs in a differentiation-dependent manner. Furthermore, several IRF proteins repress differentiation. This analysis suggests an important role for IRF proteins in adipocyte biology and demonstrates the utility of this approach in identifying cis- and trans-acting factors not previously suspected to participate in adipogenesis.

Publication types

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

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Adipogenesis / genetics*
  • Animals
  • Base Sequence
  • Binding Sites / genetics
  • Cell Differentiation / genetics
  • Chromatin Immunoprecipitation
  • Deoxyribonucleases / metabolism
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation*
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism
  • Interferon Regulatory Factors / physiology*
  • Mice
  • Polymerase Chain Reaction / methods
  • Protein Binding
  • Transcription, Genetic

Substances

  • Interferon Regulatory Factors
  • Deoxyribonucleases