TY - JOUR
T1 - Alternative mRNA splicing of corepressors generates variants that play opposing roles in adipocyte differentiation
AU - Goodson, Michael L.
AU - Mengeling, Brenda J.
AU - Jonas, Brian
AU - Privalsky, Martin L.
PY - 2011/12/30
Y1 - 2011/12/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84455161762&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84455161762&partnerID=8YFLogxK
U2 - 10.1074/jbc.M111.291625
DO - 10.1074/jbc.M111.291625
M3 - Article
C2 - 22065574
AN - SCOPUS:84455161762
VL - 286
SP - 44988
EP - 44999
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 52
ER -