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.
|Authors||Ramakrishnan, S. N.; Lau, P.; Crowther, L. M.; Cleasby, M. E.; Millard, S.; Leong, G. M.; Cooney, G. J.; Muscat, G. E.;|
|Publisher Name||BIOCHEM BIOPH RES CO|
|Published Date||2009-01-01 00:00:00|
|OpenAccess Link||https://publications.gimr.garvan.org.au/download.php?10478_10683/09 Ramakrishnan.pdf|