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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Vydané v:	Cell Ročník 142; číslo 6; s. 943
Hlavní autori:	Asher, Gad, Reinke, Hans, Altmeyer, Matthias, Gutierrez-Arcelus, Maria, Hottiger, Michael O, Schibler, Ueli
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 17.09.2010
Predmet:	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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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.
AbstractList	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.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. 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.
Author	Gutierrez-Arcelus, Maria Reinke, Hans Hottiger, Michael O Asher, Gad Schibler, Ueli Altmeyer, Matthias
Author_xml	– sequence: 1 givenname: Gad surname: Asher fullname: Asher, Gad email: gad.asher@unige.ch organization: Department of Molecular Biology, University of Geneva, 1211 Geneva 4, Switzerland. gad.asher@unige.ch – sequence: 2 givenname: Hans surname: Reinke fullname: Reinke, Hans – sequence: 3 givenname: Matthias surname: Altmeyer fullname: Altmeyer, Matthias – sequence: 4 givenname: Maria surname: Gutierrez-Arcelus fullname: Gutierrez-Arcelus, Maria – sequence: 5 givenname: Michael O surname: Hottiger fullname: Hottiger, Michael O – sequence: 6 givenname: Ueli surname: Schibler fullname: Schibler, Ueli
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SubjectTerms	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
Title	Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding
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