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Molecular components of the circadian clock in mammals
Author(s) -
Takahashi J. S.
Publication year - 2015
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12514
Subject(s) - circadian clock , cryptochrome , rna polymerase ii , biology , circadian rhythm , chromatin , microbiology and biotechnology , histone h3 , transcription (linguistics) , histone , genetics , promoter , gene , gene expression , neuroscience , linguistics , philosophy
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 .