Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding

Circadian clocks in peripheral organs are tightly coupled to cellular metabolism and are readily entrained by feeding-fasting cycles. However, the molecular mechanisms involved are largely unknown. Here we show that in liver the activity of PARP-1, an NAD(+)-dependent ADP-ribosyltransferase, oscilla...

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Veröffentlicht in:Cell Jg. 142; H. 6; S. 943
Hauptverfasser: Asher, Gad, Reinke, Hans, Altmeyer, Matthias, Gutierrez-Arcelus, Maria, Hottiger, Michael O, Schibler, Ueli
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 17.09.2010
Schlagworte:
Animals
Biological Clocks
Circadian Rhythm
Circadian Rhythm Signaling Peptides and Proteins - metabolism
Feeding Behavior
Liver - metabolism
Mice
Mice, Knockout
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases - genetics
Poly(ADP-ribose) Polymerases - metabolism
ISSN:1097-4172, 1097-4172
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Zusammenfassung:Circadian clocks in peripheral organs are tightly coupled to cellular metabolism and are readily entrained by feeding-fasting cycles. However, the molecular mechanisms involved are largely unknown. Here we show that in liver the activity of PARP-1, an NAD(+)-dependent ADP-ribosyltransferase, oscillates in a daily manner and is regulated by feeding. We provide biochemical evidence that PARP-1 binds and poly(ADP-ribosyl)ates CLOCK at the beginning of the light phase. The loss of PARP-1 enhances the binding of CLOCK-BMAL1 to DNA and leads to a phase-shift of the interaction of CLOCK-BMAL1 with PER and CRY repressor proteins. As a consequence, CLOCK-BMAL1-dependent gene expression is altered in PARP-1-deficient mice, in particular in response to changes in feeding times. Our results show that Parp-1 knockout mice exhibit impaired food entrainment of peripheral circadian clocks and support a role for PARP-1 in connecting feeding with the mammalian timing system.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2010.08.016