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Rev-erb beta regulates the Srebp-1c promoter and mRNA expression in skeletal muscle cells


The nuclear hormone receptor, Rev-erb beta operates as a transcriptional silencer. We previously demonstrated that exogenous expression of Rev-erb betaDeltaE in skeletal muscle cells increased Srebp-1c mRNA expression. We validated these in vitro observations by injection of an expression vector driving Rev-erb betaDeltaE expression into mouse tibialis muscle that resulted in increased Srebp-1c mRNA expression. Paradoxically, Rev-erb beta siRNA expression in skeletal muscle cells repressed Srebp-1c expression, and indicated that Rev-erb beta expression was necessary for Srebp-1c expression. ChIP analysis demonstrated that Rev-erb beta was recruited to the Srebp-1c promoter. Moreover, Rev-erb beta trans-activated the Srebp-1c promoter, in contrast, Rev-erb beta efficiently repressed the Rev-erb alpha promoter, a previously characterized target gene. Finally, treatment with the Rev-erb agonist (hemin) (i) increased the trans-activation of the Srebp-1c promoter by Rev-erb beta; and (ii) increased Rev-erb beta and Srebp-1c mRNA expression. These data suggest that Rev-erb beta has the potential to activate gene expression, and is a positive regulator of Srebp-1c, a regulator of lipogenesis.

Type Journal
ISBN 1090-2104 (Electronic)
Authors Ramakrishnan, S. N.; Lau, P.; Crowther, L. M.; Cleasby, M. E.; Millard, S.; Leong, G. M.; Cooney, G. J.; Muscat, G. E.;
Published Date 2009-01-01
Published Volume 388
Published Issue 4
Published Pages 654-9
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version