Transcriptional Architecture and Chromatin Landscape of the Core Circadian Clock in Mammals

By Nobuya Koike, Seung-Hee Yoo, Hung-Chung Huang, Vivek Kumar, Choogon Lee, Tae-Kyung Kim, J. Takahashi. Science, 2012

1,374 citations recorded by the source corpus.

Transcription Around the Clock The biological clock that controls daily rhythms in mammalian physiology and behavior is thought to be regulated in large part by transcriptional events (see the Perspective by Doherty and Kay). Koike et al. (p. 349; published online 30 August) produced a comprehensive analysis of these transcriptional events across the entire mouse liver genome over a 24-hour period. Only ∼22% of cycling messenger RNA transcripts were driven by de novo transcription, suggesting that posttranscriptional events also play an important regulatory role in the mammalian clock. Biological timing in organisms can also respond to rhythmic cues from the environment. Morf et al. (p. 379, published online 23 August) explored how one such cue, cycles in ambient temperature, influence circadian timing in mammalian cells. Cold-inducible RNA–binding protein (CIRP) accumulates when body temperature is low. A systematic search for binding partners of CIRP identified RNA encoding core components of the circadian clock. Loss of CIRP decreased the amplitude of circadian gene expression and cells lacking CIRP adapted more quickly to temperature cycles. A 1-day reconstruction of transcriptional events reveals the influence of the circadian clock across the genome. 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.

Subfields: Aging, Endocrine and Autonomic Systems, Plant Science

View Paper: https://www.semanticscholar.org/paper/906bae4173d2f9c9ad6ecaa514dd53e523f4d53f

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Citations in the corpus

T cell metabolism drives immunity (2015, background): “Acetylation also affects the activity of circadian clock proteins, and reciprocally, the circadian acetylome has been found to regulate the epigenome and mitochondrial metabolic pathways (Koike et al., 2012; Lu and Thompson, 2012; Masri et al., 2013).”
Molecular components of the Mammalian circadian clock. (2013, background): “Our laboratory has recently interrogated on a genome-wide level the cis-acting regulatory elements (cistrome) of the entire CLOCK/BMAL1 transcriptional feedback loop in the mouse liver (Koike et al. 2012).”
Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations. (2016, neutral): “These factors control rhythmic chromatin dynamics, including rhythmic changes in epigenetic marks at circadian promoters, spatial chromosome arrangement, and polymerase activity, thereby determining the fraction of the genome undergoing oscillating expression in a tissue-specific manner (Aguilar-Arn”
RNA-methylation-dependent RNA processing controls the speed of the circadian clock. (2013, neutral): “More recent RNA-sequencing data have shown that, of these rhythmic genes, only about a fifth is driven by de novo transcription (Koike et al., 2012).”
Reprogramming of the Circadian Clock by Nutritional Challenge (2013, positive): “At the cellular level, these rhythms are controlled by transcriptional feedback loops that produce oscillations in gene expression, a process associated with circadian changes in chromatin architecture, mRNA processing, protein activity and turnover (Feng and Lazar, 2012) (Koike et al., 2012; Morf e”
Metabolic Regulation of Gene Expression by Histone Lysine β-hydroxybutyrylation (2016, positive): “Consistently, we found a positive correlation between H3K9bhb and RNA Pol II (Ser5p) occupancy at TSSs (Figure S4C), when comparing H3K9bhb ChIP-seq data and published Pol II (Ser5p) ChIP-seq data in mouse liver (Koike et al., 2012).”
A circadian gene expression atlas in mammals: Implications for biology and medicine (2014, methodology): “Recent studies have found additional layers of complexity in hepatic rhythms by examining DNA binding patterns of core clock genes, changes in epigenetic marks, and oscillations in the proteome (9, 10, 26, 32).”
Molecular Architecture of the Mammalian Circadian Clock (2013, background): “CLOCK:BMAL1 binding occurs primarily at consensus E-box DNA motifs and recruits complexes of the integral clock protein transcriptional repressors PER1, PER2, CRY1, and CRY2, with peak occupancy in the evening at CT15–18 [39].”