A Circadian Rhythm Orchestrated by Histone Deacetylase 3 Controls Hepatic Lipid Metabolism

Mar 12, 2011Science (New York, N.Y.)

A daily biological clock controlled by histone deacetylase 3 regulates liver fat metabolism

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Abstract

Histone deacetylase 3 (HDAC3) shows a circadian rhythm in its recruitment to the genome in mouse liver.

  • Circadian disruption may worsen metabolic diseases like obesity and diabetes.
  • Histone acetylation levels are inversely related to HDAC3 binding in the liver.
  • The rhythmic recruitment of HDAC3 to the genome is lost in its absence.
  • HDAC3 recruitment correlates with the expression of the circadian nuclear receptor Rev-erbα.
  • Colocalization of Rev-erbα and HDAC3 occurs near genes that regulate lipid metabolism.
  • Deletion of either HDAC3 or Rev-erbα in mouse liver can lead to fatty liver disease.

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