Systems Chronobiology: Global Analysis of Gene Regulation in a 24-Hour Periodic World

J, Mermet; Yeung, Jake; Naef, Félix

doi:10.1101/cshperspect.a028720

Cited by 44 publications

(44 citation statements)

References 142 publications

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“…TF analysis of this module notably identified TFs related to insulin biosynthesis and gluconeogenesis, such as MAFB (Matsuoka et al 2003) and EGR1 (Matsuoka et al 2003;Shen et al 2015), whose activities peaked at ZT11 and ZT3, respectively ( Figure 3B & Supplemental Figure S4A). Integrating temporal activities of candidate TFs with RNA-Seq and our previously described temporal nuclear protein dataset (Wang et al 2017), we found that rhythmic activity of MAFB and EGR1 was supported by rhythmic mRNA abundance followed by rhythmic nuclear protein abundance ( Figure 3B, Supplemental Figure S4B), likely reflecting the delayed protein abundance after mRNA accumulation (Mermet et al 2016).…”

Section: Oscillatory Tf Activity In One Tissue But Not Others Can Drimentioning

confidence: 66%

“…Individual cells within organs contain a molecular oscillator that, together with rhythmic systemic signals such as hormones, temperature, and feeding behavior, collectively drive diurnal oscillations in gene expression and physiology (Lamia et al 2008;Reinke et al 2008;Vollmers et al 2012;Cho et al 2012). Remarkably, the circadian clock impinges on many gene regulatory layers, from transcriptional and posttranscriptional processes, translation efficiency, to translational and posttranslational processes (Mermet et al 2016).…”

Section: Introductionmentioning

confidence: 99%

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Transcription factor activity rhythms and tissue-specific chromatin interactions explain circadian gene expression across organs

Yeung

Jouffe

et al. 2017

Preprint

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Temporal control of physiology requires the interplay between gene networks involved in daily timekeeping and tissue function across different organs. How the circadian clock interweaves with tissue-specific transcriptional programs is poorly understood. Here we dissected temporal and tissue-specific regulation at multiple gene regulatory layers by examining mouse tissues with an intact or disrupted clock over time. Integrated analysis uncovered two distinct regulatory modes underlying tissue-specific rhythms: tissuespecific oscillations in transcription factor (TF) activity, which were linked to feedingfasting cycles in liver and sodium homeostasis in kidney; and co-localized binding of clock and tissue-specific transcription factors at distal enhancers. Chromosome conformation capture (4C-Seq) in liver and kidney identified liver-specific chromatin loops that recruited clock-bound enhancers to promoters to regulate liver-specific transcriptional rhythms.Furthermore, this looping was remarkably promoter-specific on the scale of less than ten kilobases. Enhancers can contact a rhythmic promoter while looping out nearby nonrhythmic alternative promoters, confining rhythmic enhancer activity to specific promoters. These findings suggest that chromatin folding enables the clock to regulate rhythmic transcription of specific promoters to output temporal transcriptional programs tailored to different tissues.

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Section: Oscillatory Tf Activity In One Tissue But Not Others Can Drimentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Transcription factor activity rhythms and tissue-specific chromatin interactions explain circadian gene expression across organs

Yeung

Jouffe

et al. 2017

Preprint

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“…3B; Supplemental Fig. S4B), likely reflecting the delayed protein abundance after mRNA accumulation (Mermet et al 2016).…”

Section: Combinatorics Of Rhythmic Transcript Expression Across Tissumentioning

confidence: 99%

“…Individual cells within organs contain a molecular oscillator that, together with rhythmic systemic signals such as hormones, temperature, and feeding behavior, collectively drive diurnal oscillations in gene expression and physiology (Lamia et al 2008;Reinke et al 2008;Cho et al 2012;Vollmers et al 2012). Remarkably, the circadian clock impinges on many gene regulatory layers, from transcriptional and post-transcriptional processes, translation efficiency, to translational and post-translational processes (Mermet et al 2016).…”

mentioning

confidence: 99%

Transcription factor activity rhythms and tissue-specific chromatin interactions explain circadian gene expression across organs

et al. 2017

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Temporal control of physiology requires the interplay between gene networks involved in daily timekeeping and tissue function across different organs. How the circadian clock interweaves with tissue-specific transcriptional programs is poorly understood. Here, we dissected temporal and tissue-specific regulation at multiple gene regulatory layers by examining mouse tissues with an intact or disrupted clock over time. Integrated analysis uncovered two distinct regulatory modes underlying tissue-specific rhythms: tissue-specific oscillations in transcription factor (TF) activity, which were linked to feeding-fasting cycles in liver and sodium homeostasis in kidney; and colocalized binding of clock and tissue-specific transcription factors at distal enhancers. Chromosome conformation capture (4C-seq) in liver and kidney identified liver-specific chromatin loops that recruited clock-bound enhancers to promoters to regulate liver-specific transcriptional rhythms. Furthermore, this looping was remarkably promoter-specific on the scale of less than 10 kilobases (kb). Enhancers can contact a rhythmic promoter while looping out nearby nonrhythmic alternative promoters, confining rhythmic enhancer activity to specific promoters. These findings suggest that chromatin folding enables the clock to regulate rhythmic transcription of specific promoters to output temporal transcriptional programs tailored to different tissues.

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“…Temporal compartmentalization can prevent two opposite and incompatible processes from simultaneously occurring, for example, glucose is stored as glycogen following a meal and is later released into the blood circulation during fasting period to maintain homeostasis in plasma glucose levels. Functional genomics studies of the circadian liver were typically performed on bulk liver tissue 12 . In particular, we and others showed how both the circadian clock and the feeding fasting cycles pervasively drive rhythms of gene expression in bulk, impacting key sectors of liver physiology such as lipid and steroid metabolism 13–15 .…”

Section: Introductionmentioning

confidence: 99%

Space-time logic of liver gene expression at sublobular scale

Droin

Kholtei

Halpern

et al. 2020

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20The mammalian liver performs key physiological functions for maintaining energy and 21 metabolic homeostasis. Liver tissue is both spatially structured and temporally 22 orchestrated. Hepatocytes operate in repeating anatomical units termed lobules and 23 different lobule zones perform distinct functions. The liver is also subject to extensive 24 temporal regulation, orchestrated by the interplay of the circadian clock, systemic signals 25 and feeding rhythms. Liver zonation was previously analyzed as a static phenomenon and 26 liver chronobiology at the tissue level. Here, we use single-cell RNA-seq to investigate 27 the interplay between gene regulation in space and time. Categorizing mRNA expression 28 profiles using mixed-effect models and smFISH validations, we find that many genes in 29 the liver are both zonated and rhythmic, most of them showing multiplicative space-time 30 effects. Such dually regulated genes cover key hepatic functions such as lipid, 31 carbohydrate and amino acid metabolism. In particular, our data suggest that rhythmic 32 and localized expression of Wnt targets may be explained by rhythmic Wnt signaling 33 from endothelial cells near the central vein. Core circadian clock genes are expressed in 34 a non-zonated manner, indicating that the liver clock is robust to zonation. Together, our 35 comprehensive data reveal how liver function is compartmentalized spatio-temporally at 36 the sub-lobular scale. 37Recently, we combined single-cell RNA-sequencing (scRNA-seq) of dissociated 53 hepatocytes and single-molecule RNA fluorescence in situ hybridization (smFISH) to 54 reconstruct spatial mRNA expression profiles along the porto-central axis 7 . This analysis 55 revealed an unexpected breadth of spatial heterogeneity, with ~50% of genes showing 56 spatially non-uniform patterns. Among them, functions related to ammonia clearance, 57 carbohydrate catabolic and anabolic processes, xenobiotics detoxification, bile acid and 58 cholesterol synthesis, fatty acid metabolism, targets of the Wnt and Ras pathways, and 59 hypoxia-induced genes were strongly zonated. 60In addition to its spatial heterogeneity, the liver is also highly dynamic 61 temporally. Chronobiology studies showed that temporally gated physiological and 62 metabolic programs in the liver result from the complex interplay between the 63 endogenous circadian liver oscillator, rhythmic systemic signals, and feeding/fasting 64 cycles 8,9,10 . An intact circadian clock has repeatedly been demonstrated as key for healthy 65 metabolism, also in humans 11 . Temporal compartmentalization can prevent two opposite 66 and incompatible processes from simultaneously occurring, for example, glucose is 67 stored as glycogen following a meal and is later released into the blood circulation during 68 fasting period to maintain homeostasis in plasma glucose levels. Functional genomics 69 studies of the circadian liver were typically performed on bulk liver tissue 12 . 70In particular, we and others showed how both the circadian clock and the fee...

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Systems Chronobiology: Global Analysis of Gene Regulation in a 24-Hour Periodic World

Cited by 44 publications

References 142 publications

Transcription factor activity rhythms and tissue-specific chromatin interactions explain circadian gene expression across organs

Transcription factor activity rhythms and tissue-specific chromatin interactions explain circadian gene expression across organs

Transcription factor activity rhythms and tissue-specific chromatin interactions explain circadian gene expression across organs

Space-time logic of liver gene expression at sublobular scale

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