Diurnal regulation of RNA polymerase III transcription is under the control of both the feeding-fasting response and the circadian clock.
RNA polymerase III (Pol III) synthesizes short noncoding RNAs, many of which are essential for translation. Accordingly, Pol III activity is tightly regulated with cell growth and proliferation by factors such as MYC, RB1, TRP53, and MAF1. MAF1 is a repressor of Pol III transcription whose activity is controlled by phosphorylation; in particular, it is inactivated through phosphorylation by the TORC1 kinase complex, a sensor of nutrient availability. Pol III regulation is thus sensitive to environmental cues, yet a diurnal profile of Pol III transcription activity is so far lacking. Here, we first use gene expression arrays to measure mRNA accumulation during the diurnal cycle in the livers of (1) wild-type mice, (2) arrhythmicArntlknockout mice, (3) mice fed at regular intervals during both night and day, and (4) mice lacking theMaf1gene, and so provide a comprehensive view of the changes in cyclic mRNA accumulation occurring in these different systems. We then show that Pol III occupancy of its target genes rises before the onset of the night, stays high during the night, when mice normally ingest food and when translation is known to be increased, and decreases in daytime. Whereas higher Pol III occupancy during the night reflects a MAF1-dependent response to feeding, the rise of Pol III occupancy before the onset of the night reflects a circadian clock-dependent response. Thus, Pol III transcription during the diurnal cycle is regulated both in response to nutrients and by the circadian clock, which allows anticipatory Pol III transcription.
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.
François
F
Mange
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.|Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
Viviane
V
Praz
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.|Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
Eugenia
E
Migliavacca
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Ian M
IM
Willis
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.|Bioinformatics Core Facility, Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
Frédéric
F
Schütz
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.
Nouria
N
Hernandez
D056930:ARNTL Transcription Factors / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D004435:Eating / Q000235:genetics; D005215:Fasting / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D012320:RNA Polymerase III / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics*; D015398:Signal Transduction; D014158:Transcription, Genetic
D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; C529453:Maf1 protein, mouse; D012097:Repressor Proteins; D012320:RNA Polymerase III