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.
Ramakrishnan
Sathiya N
SN
The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072, Australia.
Lau
Patrick
P
Crowther
Lisa M
LM
Cleasby
Mark E
ME
Millard
Susan
S
Leong
Gary M
GM
Cooney
Gregory J
GJ
Muscat
George E O
GE
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018274:Electroporation; D006427:Hemin / Q000494:pharmacology; D006614:Hindlimb; D050155:Lipogenesis / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D015533:Transcriptional Activation
C499650:Nr1d2 protein, mouse; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D006427:Hemin