Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 286, Issue 11, Pages 9063-9070Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.164558
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Funding
- National Institutes of Health [1-DP2-OD006740, DK73697, CA20535, HL59596, T32 DK007217-35, GM 56847]
- Stanford Dean's Fellowship
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Glucocorticoids rapidly and robustly induce cell fate decisions in various multipotent cells, although the precise mechanisms of these important cellular events are not understood. Here we showed that glucocorticoids repressed Per3 expression and that this repression was critical for advancing mesenchymal stem cells to the adipocyte fate. Exogenous expression of Per3 inhibited adipogenesis, whereas knocking out Per3 enhanced that fate. Moreover, we found that PER3 formed a complex with PPAR gamma and inhibited PPAR gamma-mediated transcriptional activation via Ppar gamma response elements. Consistent with these findings, Per3 knock-out mice displayed alterations in body composition, with both increased adipose and decreased muscle tissue compared with wild-type mice. Our findings identify Per3 as potent mediator of cell fate that functions by altering the transcriptional activity of PPAR gamma.
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