Alternative mRNA splicing of corepressors generates variants that play opposing roles in adipocyte differentiation

Michael L. Goodson, Brenda J. Mengeling, Brian Jonas, Martin L. Privalsky

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The SMRT and NCoR corepressors partner with, and help mediate repression by, a wide variety of nuclear receptors and non-receptor transcription factors. Both SMRT and NCoR are expressed by alternative mRNA splicing, resulting in the production of a series of interrelated corepressor variants that differ in their tissue distribution and in their biochemical properties. We report here that different corepressor splice variants can exert opposing transcriptional and biological effects during adipocyte differentiation. Most notably, the NCoRω splice variant inhibits, whereas the NCoRδ splice variant promotes, adipogenesis. Furthermore, the ratio of NCoRω to NCoRδ decreases during adipogenic differentiation. We propose that this alteration in corepressor splicing helps convert the cellular transcriptional program from one that maintains the pre-adipocyte in an undifferentiated state to a new transcriptional context that promotes differentiation and helps establish the proper physiology of the mature adipocyte.

Original languageEnglish (US)
Pages (from-to)44988-44999
Number of pages12
JournalJournal of Biological Chemistry
Volume286
Issue number52
DOIs
StatePublished - Dec 30 2011

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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