کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1932950 | 1050598 | 2009 | 6 صفحه PDF | دانلود رایگان |
The nuclear hormone receptor, Rev-erb beta operates as a transcriptional silencer. We previously demonstrated that exogenous expression of Rev-erbβΔE in skeletal muscle cells increased Srebp-1c mRNA expression. We validated these in vitro observations by injection of an expression vector driving Rev-erbβΔE expression into mouse tibialis muscle that resulted in increased Srebp-1c mRNA expression. Paradoxically, Rev-erbβ siRNA expression in skeletal muscle cells repressed Srebp-1c expression, and indicated that Rev-erbβ expression was necessary for Srebp-1c expression. ChIP analysis demonstrated that Rev-erbβ was recruited to the Srebp-1c promoter. Moreover, Rev-erbβ trans-activated the Srebp-1c promoter, in contrast, Rev-erbβ efficiently repressed the Rev-erbα 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-erbβ; and (ii) increased Rev-erbβ and Srebp-1c mRNA expression. These data suggest that Rev-erbβ has the potential to activate gene expression, and is a positive regulator of Srebp-1c, a regulator of lipogenesis.
Journal: Biochemical and Biophysical Research Communications - Volume 388, Issue 4, 30 October 2009, Pages 654–659