Molecular components of the circadian clock in mammals.
The circadian clock mechanism in animals involves a transcriptional feedback loop in which the bHLH-PAS proteins CLOCK and BMAL1 form a transcriptional activator complex to activate the transcription of the Period and Cryptochrome genes, which in turn feed back to repress their own transcription. In the mouse liver, CLOCK and BMAL1 interact with the regulatory regions of thousands of genes, which are both cyclically and constitutively expressed. The circadian transcription in the liver is clustered in phase and this is accompanied by circadian occupancy of RNA polymerase II recruitment and initiation. These changes also lead to circadian fluctuations in histone H3 lysine4 trimethylation (H3K4me3) as well as H3 lysine9 acetylation (H3K9ac) and H3 lysine27 acetylation (H3K27ac). Thus, the circadian clock regulates global transcriptional poise and chromatin state by regulation of RNA polymerase II.
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.|Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.
J S
JS
Takahashi
D056930:ARNTL Transcription Factors / Q000235:genetics* / Q000502:physiology; D000107:Acetylation; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D056926:CLOCK Proteins / Q000235:genetics* / Q000502:physiology; D057906:Circadian Clocks / Q000235:genetics*; D015870:Gene Expression; D006657:Histones / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000502:physiology; D008239:Lysine / Q000378:metabolism; D008322:Mammals / Q000235:genetics*; D051379:Mice; D008954:Models, Biological; D012319:RNA Polymerase II / Q000378:metabolism; D014158:Transcription, Genetic
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D006657:Histones; D008239:Lysine; D012319:RNA Polymerase II
ChIP-seq; Clock gene; RNA polymerase II; RNA-seq; chromatin; circadian clock; epigenetics; histone modifications; transcription