HNF6 and Rev-erbα integrate hepatic lipid metabolism by overlapping and distinct transcriptional mechanisms.

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  • Additional Information
    • Source:
      Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 8711660 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1549-5477 (Electronic) Linking ISSN: 08909369 NLM ISO Abbreviation: Genes Dev Subsets: MEDLINE
    • Publication Information:
      Publication: Cold Spring Harbor, NY : Cold Spring Harbor Laboratory Press
      Original Publication: [Cold Spring Harbor, N.Y.] : Cold Spring Harbor Laboratory in association with the Genetical Society of Great Britain, [c1987-
    • Subject Terms:
      Gene Expression Regulation/*genetics ; Hepatocyte Nuclear Factor 6/*genetics ; Hepatocyte Nuclear Factor 6/*metabolism ; Lipid Metabolism/*genetics ; Liver/*metabolism ; Liver/*physiopathology ; Nuclear Receptor Subfamily 1, Group D, Member 1/*metabolism; Animals ; Fatty Liver/genetics ; Gene Deletion ; Gene Knockout Techniques ; Male ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group D, Member 1/genetics ; Protein Binding/genetics
    • Abstract:
      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 C57Bl/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-erbα, and binding of Rev-erbα at these sites was lost when HNF6 was ablated in the liver. While HNF6 and Rev-erbα 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.
      (© 2016 Zhang et al.; Published by Cold Spring Harbor Laboratory Press.)
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    • Grant Information:
      R01 DK045586 United States DK NIDDK NIH HHS; R01 DK105689 United States DK NIDDK NIH HHS; P30 DK050306 United States DK NIDDK NIH HHS; U01 DK089540 United States DK NIDDK NIH HHS; T32 GM008216 United States GM NIGMS NIH HHS; P30 DK019525 United States DK NIDDK NIH HHS
    • Contributed Indexing:
      Keywords: HNF6; Onecut; Rev-erbα; integrative physiology; lipid metabolism; liver; steatosis
    • Accession Number:
      0 (Hepatocyte Nuclear Factor 6)
      0 (Nr1d1 protein, mouse)
      0 (Nuclear Receptor Subfamily 1, Group D, Member 1)
    • Publication Date:
      Date Created: 20160723 Date Completed: 20170512 Latest Revision: 20181113
    • Publication Date:
      20221213
    • Accession Number:
      PMC4973293
    • Accession Number:
      10.1101/gad.281972.116
    • Accession Number:
      27445394