title: Transcriptional architecture and chromatin landscape of the core circadian clock in mammals.
abstract: The mammalian circadian clock involves a transcriptional feed back loop in which CLOCK and BMAL1 activate the Period and Cryptochrome genes, which then feedback and repress their own transcription. We have interrogated the transcriptional architecture of the circadian transcriptional regulatory loop on a genome scale in mouse liver and find a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II (RNAPII) recruitment, RNA expression, and chromatin states. We find that the circadian transcriptional cycle of the clock consists of three distinct phases: a poised state, a coordinated de novo transcriptional activation state, and a repressed state. Only 22% of messenger RNA (mRNA) cycling genes are driven by de novo transcription, suggesting that both transcriptional and posttranscriptional mechanisms underlie the mammalian circadian clock. We also find that circadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling.
authors.affiliation: Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Koike
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Yoo
authors.forename: Hung-Chung
authors.initials: HC
authors.lastname: Huang
authors.forename: Vivek
authors.initials: V
authors.lastname: Kumar
authors.forename: Choogon
authors.initials: C
authors.lastname: Lee
authors.forename: Tae-Kyung
authors.initials: TK
authors.lastname: Kim
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Takahashi
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism; D000818:Animals; D056926:CLOCK Proteins / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D057906:Circadian Clocks / Q000235:genetics*; D056931:Cryptochromes / Q000235:genetics*; D021901:DNA, Intergenic; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D056426:Genetic Loci; D006657:Histones / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D056950:Period Circadian Proteins / Q000235:genetics; D012319:RNA Polymerase II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D002843:Chromatin; D056931:Cryptochromes; D021901:DNA, Intergenic; D006657:Histones; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D056926:CLOCK Proteins; C538944:Clock protein, mouse; D012319:RNA Polymerase II