Circadian Regulator CLOCK Is a Histone Acetyltransferase

@article{Doi2006CircadianRC,
  title={Circadian Regulator CLOCK Is a Histone Acetyltransferase},
  author={Masao Doi and Jun Hirayama and Paolo Sassone-Corsi},
  journal={Cell},
  year={2006},
  volume={125},
  pages={497-508}
}
The molecular machinery that governs circadian rhythmicity comprises proteins whose interplay generates time-specific transcription of clock genes. The role of chromatin remodeling in a physiological setting such as the circadian clock is yet unclear. We show that the protein CLOCK, a central component of the circadian pacemaker, has histone acetyltransferase (HAT) activity. CLOCK shares homology with acetyl-coenzyme A binding motifs within the MYST family of HATs. CLOCK displays high sequence… Expand
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It is shown that CLOCK also acetylates a non-histone substrate: its own partner, BMAL1, is specifically acetylated on a unique, highly conserved Lys 537 residue, revealing the enzymatic interplay between two clock core components is crucial for the circadian machinery. Expand
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TLDR
A specialized program of chromatin remodeling appears to be at the core of the circadian machinery, transducing signals originated by cellular metabolites to the circadian clock. Expand
The NAD+-Dependent Deacetylase SIRT1 Modulates CLOCK-Mediated Chromatin Remodeling and Circadian Control
TLDR
It is proposed that SIRT1 functions as an enzymatic rheostat of circadian function, transducing signals originated by cellular metabolites to the circadian clock. Expand
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TLDR
Research over the past decade has unveiled an exquisitely dynamic genome that is appropriately phased to anticipate oscillating environmental conditions. Expand
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TLDR
A search for the histone deacetylase (HDAC) that counterbalances CLOCK activity revealed that SIRT1, a nicotinamide adenin dinucleotide (NAD+)-dependent HDAC, functions in a circadian manner, and is a regulator of aging, inflammation and metabolism. Expand
Phosphorylation of LSD1 by PKCα is crucial for circadian rhythmicity and phase resetting.
TLDR
Evidence is provided that the lysine-specific demethylase 1 (LSD1) is phosphorylated by protein kinase Cα (PKCα) in a circadian manner and theosphorylated LSD1 forms a complex with CLOCK:BMAL1 to facilitate E-box-mediated transcriptional activation. Expand
The time of metabolism: NAD+, SIRT1, and the circadian clock.
TLDR
A search for the histone deacetylase that counterbalanced CLOCK activity revealed that SIRT1, a nicotinamide adenine dinucleotide (NAD(+))-dependent HDAC, functions in a circadian manner and was found to interact with CLOCK and to be recruited to circadian promoters in a cyclic manner. Expand
Circadian rhythms: Setting the clock
TLDR
By showing that CLock is a HAT, Sassone-Corsi and colleagues have linked the histone-acetylationmediated transcriptional regulation of circadian genes with the known circadian molecular machinery and suggest that CLOCK might be a good target for pharmaceutical agents aimed at regulating the authors' circadian rhythms and sleeping patterns. Expand
The epigenetic language of circadian clocks.
TLDR
Evidence demonstrating that chromatin remodeling is at the crossroads of circadian rhythms and regulation of metabolism and cellular proliferation is discussed. Expand
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