Abstract:
:Circadian rhythms regulate a wide variety of physiological and metabolic processes. The clock machinery comprises complex transcriptional-translational feedback loops that, through the action of specific transcription factors, modulate the expression of as many as 10% of cellular transcripts. This marked change in gene expression necessarily implicates a global regulation of chromatin remodeling. Indeed, various descriptive studies have indicated that histone modifications occur at promoters of clock-controlled genes (CCGs) in a circadian manner. The finding that CLOCK, a transcription factor crucial for circadian function, has intrinsic histone acetyl transferase (HAT) activity has paved the way to unraveling the molecular mechanisms that govern circadian chromatin remodeling. 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. Importantly, SIRT1 is a regulator of aging, inflammation and metabolism. As many transcripts that oscillate in mammalian peripheral tissues encode proteins that have central roles in metabolic processes, these findings establish a functional and molecular link between energy balance, chromatin remodeling and circadian physiology. Here we review recent studies that support the existence of this link and discuss their implications for understanding mammalian physiology and pathology.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Bellet MM,Sassone-Corsi Pdoi
10.1242/jcs.051649subject
Has Abstractpub_date
2010-11-15 00:00:00pages
3837-48issue
Pt 22eissn
0021-9533issn
1477-9137pii
123/22/3837journal_volume
123pub_type
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journal_title:Journal of cell science
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journal_title:Journal of cell science
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journal_title:Journal of cell science
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pub_type: 杂志文章
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
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journal_title:Journal of cell science
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journal_title:Journal of cell science
pub_type: 杂志文章
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journal_title:Journal of cell science
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journal_title:Journal of cell science
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