期刊
GENES & DEVELOPMENT
卷 30, 期 14, 页码 1636-1644出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.281972.116
关键词
HNF6; Onecut; liver; steatosis; lipid metabolism; integrative physiology; Rev-erb alpha
资金
- National Institutes of Health [R01 DK45586, U01 DK089540, R01DK105689]
- Cox Medical Research Institute
Hepatocyte nuclear factor 6 (HNF6) is required for liver development, but its role in adult liver metabolism is not known. Here we show that deletion of HNF6 in livers of adult C57B1/6 mice leads to hepatic steatosis in mice fed normal laboratory chow. Although HNF6 is known mainly as a transcriptional activator, hepatic loss of HNF6 up regulated many lipogenic genes bound directly by HNF6. Many of these genes are targets of the circadian nuclear receptor Rev-erb alpha, and binding of Rev-erb alpha at these sites was lost when HNF6 was ablated in the liver. While HNF6 and Rev-erb alpha coordinately regulate hepatic lipid metabolism, each factor also affects additional gene sets independently. These findings highlight a novel mechanism of transcriptional repression by HNF6 and demonstrate how overlapping and distinct mechanisms of transcription factor function contribute to the integrated physiology of the liver.
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