Class IIa histone deacetylases are key regulators of the body’s internal clock

Overexpression of HDAC5 disrupts transcriptional rhythms of core clock genes in mouse fibroblasts.

• Class IIa histone deacetylases are involved in regulating circadian behavioral rhythms in Drosophila and cellular rhythms in mammalian cells.
• In mouse fibroblasts, HDAC5 overexpression leads to decreased acetylation of the core clock protein BMAL1.
• Cyclical movement of HDAC5 between the nucleus and cytoplasm occurs in a circadian manner in mouse fibroblasts.
• Mutation of the Drosophila homolog HDAC4 reduces locomotor activity rhythms and period mRNA levels in flies.
• Knockdown of HDAC4 in Drosophila clock cells impairs circadian function.
• Class IIa HDACs may integrate extracellular signals, such as Ca(2+) and cAMP, into the regulation of the molecular clock.

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