title: Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding.
abstract: 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.
authors.affiliation: Department of Molecular Biology, University of Geneva, 1211 Geneva 4, Switzerland. gad.asher@unige.ch
authors.forename: Gad
authors.initials: G
authors.lastname: Asher
authors.forename: Hans
authors.initials: H
authors.lastname: Reinke
authors.forename: Matthias
authors.initials: M
authors.lastname: Altmeyer
authors.forename: Maria
authors.initials: M
authors.lastname: Gutierrez-Arcelus
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hottiger
authors.forename: Ueli
authors.initials: U
authors.lastname: Schibler
mesh_terms: D000818:Animals; D001683:Biological Clocks; D002940:Circadian Rhythm; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000378:metabolism; D005247:Feeding Behavior; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*
chemical_list: D056925:Circadian Rhythm Signaling Peptides and Proteins; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases