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

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 NCoR? splice variant inhibits, whereas the NCoR? splice variant promotes, adipogenesis. Furthermore, the ratio of NCoR? to NCoR? 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.

SUBMITTER: Goodson ML 

PROVIDER: S-EPMC3247966 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature