title: Genome-wide RNA polymerase II profiles and RNA accumulation reveal kinetics of transcription and associated epigenetic changes during diurnal cycles.
abstract: Interactions of cell-autonomous circadian oscillators with diurnal cycles govern the temporal compartmentalization of cell physiology in mammals. To understand the transcriptional and epigenetic basis of diurnal rhythms in mouse liver genome-wide, we generated temporal DNA occupancy profiles by RNA polymerase II (Pol II) as well as profiles of the histone modifications H3K4me3 and H3K36me3. We used these data to quantify the relationships of phases and amplitudes between different marks. We found that rhythmic Pol II recruitment at promoters rather than rhythmic transition from paused to productive elongation underlies diurnal gene transcription, a conclusion further supported by modeling. Moreover, Pol II occupancy preceded mRNA accumulation by 3 hours, consistent with mRNA half-lives. Both methylation marks showed that the epigenetic landscape is highly dynamic and globally remodeled during the 24-hour cycle. While promoters of transcribed genes had tri-methylated H3K4 even at their trough activity times, tri-methylation levels reached their peak, on average, 1 hour after Pol II. Meanwhile, rhythms in tri-methylation of H3K36 lagged transcription by 3 hours. Finally, modeling profiles of Pol II occupancy and mRNA accumulation identified three classes of genes: one showing rhythmicity both in transcriptional and mRNA accumulation, a second class with rhythmic transcription but flat mRNA levels, and a third with constant transcription but rhythmic mRNAs. The latter class emphasizes widespread temporally gated posttranscriptional regulation in the mouse liver.
authors.affiliation: Department of Molecular Biology, University of Geneva, Geneva, Switzerland.
authors.forename: Gwendal
authors.initials: G
authors.lastname: Le Martelot
authors.forename: Donatella
authors.initials: D
authors.lastname: Canella
authors.forename: Laura
authors.initials: L
authors.lastname: Symul
authors.forename: Eugenia
authors.initials: E
authors.lastname: Migliavacca
authors.forename: Federica
authors.initials: F
authors.lastname: Gilardi
authors.forename: Robin
authors.initials: R
authors.lastname: Liechti
authors.forename: Olivier
authors.initials: O
authors.lastname: Martin
authors.forename: Keith
authors.initials: K
authors.lastname: Harshman
authors.forename: Mauro
authors.initials: M
authors.lastname: Delorenzi
authors.forename: Béatrice
authors.initials: B
authors.lastname: Desvergne
authors.forename: Winship
authors.initials: W
authors.lastname: Herr
authors.forename: Bart
authors.initials: B
authors.lastname: Deplancke
authors.forename: Ueli
authors.initials: U
authors.lastname: Schibler
authors.forename: Jacques
authors.initials: J
authors.lastname: Rougemont
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guex
authors.forename: Nouria
authors.initials: N
authors.lastname: Hernandez
authors.forename: Felix
authors.initials: F
authors.lastname: Naef
mesh_terms: D000818:Animals; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D002940:Circadian Rhythm; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006207:Half-Life; D006657:Histones / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D006657:Histones; D012333:RNA, Messenger; D012319:RNA Polymerase II