PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator

Steven A Brown; Juergen Ripperger; Sebastian Kadener; Fabienne Fleury-Olela; Francis Vilbois; Michael Rosbash; Ueli Schibler

doi:10.1126/science.1107373

PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator

Science. 2005 Apr 29;308(5722):693-6. doi: 10.1126/science.1107373.

Authors

Steven A Brown¹, Juergen Ripperger, Sebastian Kadener, Fabienne Fleury-Olela, Francis Vilbois, Michael Rosbash, Ueli Schibler

Affiliation

¹ Department of Molecular Biology and National Centres of Competence in Research (NCCR) Frontiers in Genetics, Sciences III, University of Geneva, 30 Quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland. steven.brown@molbio.unige.ch

PMID: 15860628
DOI: 10.1126/science.1107373

Abstract

The clock proteins PERIOD1 (PER1) and PERIOD2 (PER2) play essential roles in a negative transcriptional feedback loop that generates circadian rhythms in mammalian cells. We identified two PER1-associated factors, NONO and WDR5, that modulate PER activity. The reduction of NONO expression by RNA interference (RNAi) attenuated circadian rhythms in mammalian cells, and fruit flies carrying a hypomorphic allele were nearly arrhythmic. WDR5, a subunit of histone methyltransferase complexes, augmented PER-mediated transcriptional repression, and its reduction by RNAi diminished circadian histone methylations at the promoter of a clock gene.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells
Animals
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cell Cycle Proteins
Cell Line
Circadian Rhythm*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Drosophila / genetics
Drosophila / physiology
Drosophila Proteins / genetics
Drosophila Proteins / physiology
Female
Gene Expression Regulation
Histones / metabolism
Immunoprecipitation
Intracellular Signaling Peptides and Proteins
Male
Methylation
Mice
Mice, Inbred BALB C
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Nuclear Proteins / physiology
Nuclear Receptor Subfamily 1, Group D, Member 1
Period Circadian Proteins
Promoter Regions, Genetic
Proteins / genetics
Proteins / metabolism*
RNA Interference
RNA-Binding Proteins
Rats
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism
Transcription Factors
Transcription, Genetic
Transfection

Substances

Carrier Proteins
Cell Cycle Proteins
DNA-Binding Proteins
Drosophila Proteins
Histones
Intracellular Signaling Peptides and Proteins
NONA protein, Drosophila
Nono protein, mouse
Nr1d1 protein, mouse
Nr1d1 protein, rat
Nuclear Proteins
Nuclear Receptor Subfamily 1, Group D, Member 1
Per1 protein, mouse
Per1 protein, rat
Per2 protein, mouse
Per2 protein, rat
Period Circadian Proteins
Proteins
RNA-Binding Proteins
Receptors, Cytoplasmic and Nuclear
Transcription Factors
Wdr5 protein, mouse