Oscillating and stable promoter-enhancer loops underlie core- and clock-controlled gene expression rhythms in mouse liver
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE139195 | GEO | 2020/12/18
REPOSITORIES: GEO
Similar Datasets
Project description:Oscillating and stable promoter-enhancer loops underlie core- and clock-controlled gene expression rhythms in mouse liver
| PRJNA578734 | ENA
Project description:The circadian clock drives extensive temporal gene expression programs controlling daily changes in behavior and physiology. In mouse liver, transcription factors dynamics, chromatin modifications, and RNA Polymerase II (PolII) activity oscillate throughout the 24-hour (24h) day, regulating the rhythmic synthesis of thousands of transcripts. Also, 24h rhythms in gene promoter-enhancer chromatin looping accompany rhythmic mRNA synthesis. However, how chromatin organization impinges on temporal transcription and liver physiology remains unclear. Here, we applied time-resolved chromosome conformation capture (4C-seq) in livers of WT and arrhythmic Bmal1 knockout mice. In WT, we observed 24h oscillations in promoter-enhancer loops at multiple loci including the core-clock genes Period1, Period2 and Bmal1. In addition, we detected rhythmic PolII activity, chromatin modifications and transcription involving stable chromatin loops at clock-output gene promoters representing key liver function such as glucose metabolism and detoxification. Intriguingly, these contacts persisted in clock-impaired mice in which both PolII activity and chromatin marks no longer oscillated. Finally, we observed chromatin interaction hubs connecting neighbouring genes showing coherent transcription regulation across genotypes. Thus, both clock-controlled and clock-independent chromatin topology underlie rhythmic regulation of liver physiology.
| S-EPMC7877755 | biostudies-literature
Project description:The circadian clock dynamically rewires promoter-enhancer loops in tissues to drive robust daily rhythms in gene transcription and locomoter activity.
2018-03-26 | GSE101423 | GEO
Project description:Chromatin organization plays a crucial role in gene regulation by controlling the accessibility of DNA to transcription machinery. While significant progress has been made in understanding the regulatory role of clock proteins in circadian rhythms, how chromatin organization affects circadian rhythms remains poorly understood. Here, we employed ATAC-seq (Assay for Transposase-Accessible Chromatin with Sequencing) on FAC-sorted Drosophila clock neurons to assess genome-wide chromatin accessibility at dawn and dusk over the circadian cycle. We observed significant oscillations in chromatin accessibility at promoter and enhancer regions of hundreds of genes, with enhanced accessibility either at dusk or dawn, which correlated with their peak transcriptional activity. Notably, genes with enhanced accessibility at dusk were enriched with E-box motifs, while those more accessible at dawn were enriched with VRI/PDP1-box motifs, indicating that they are regulated by the core circadian feedback loops, PER/CLK and VRI/PDP1, respectively. Further, we observed a complete loss of chromatin accessibility rhythms in per01 null mutants, with chromatin consistently accessible at both dawn and dusk, underscoring the critical role of Period protein in driving chromatin compaction during the repression phase at dawn. Together, this study demonstrates the significant role of chromatin organization in circadian regulation, revealing how the interplay between clock proteins and chromatin structure orchestrates the precise timing of biological processes throughout the day. This work further implies that variations in chromatin accessibility might play a central role in the generation of diverse circadian gene expression patterns in clock neurons.
2024-03-05 | GSE256533 | GEO
Project description:This dataset was generated to investigate the independence of the central clock in regulating hepatic transcriptional rhythms.
2022-07-05 | GSE196430 | GEO
Project description:Observational, non randomized study aimed at measuring the circadian rhythms in the urinary concentrations of physiological modified nucleosides in 30 patients with metastatic colorectal cancer and in 30 age and sex-matched healthy subjects.
| 2132582 | ecrin-mdr-crc
Project description:Circadian (~24 hour) clocks exist in almost all types of living organism and play a fundamental role in regulating daily physiological and behavioural processes. The transcription factor BMAL1 (ARNTL) is thought to be one of the principal drivers of the molecular clock in mammals since its deletion abolishes 24-hour activity patterning, an important physiological output of the clockwork. However, whether or not Bmal1-/- mice can nevertheless display molecular 24-hour rhythms is unknown. Here, we determined whether Bmal1 function is necessary for daily molecular oscillations in two tissues – skin fibroblasts and liver. Unexpectedly, both tissues exhibited robust 24-hour oscillations over 2-3 days in the absence of any exogenous synchronizers such as daily light or temperature cycles. This demonstrates a competent 24-hour molecular pacemaker in Bmal1 knockouts. Indeed, molecular oscillations were pervasive throughout the transcriptome, proteome and phosphoproteome of Bmal1-/- mice. In particular, several proteins exhibited rhythmic phosphorylation in both Bmal1-proficient and -deficient cells, highlighting an unanticipated role for post-translational regulators in 24-hour rhythms in the absence of any known clock mechanisms.
2020-02-17 | PXD009243 | Pride
Project description:Ketone bodies, intermediates in energy metabolism and signaling, have attracted significant attention due to their role in health and disease. We performed around the clock study on ketone bodies and ketogenesis with mice on different diets. We found that caloric restriction, a dietary intervention that improves metabolism and longevity, induced high amplitude circadian rhythms in blood βOHB. The blood βOHB rhythms resulted from rhythmic ketogenesis in the liver controlled by the interaction between the circadian clock and PPAR transcriptional networks. This interaction results in transcriptional reprogramming of in beta-oxidation and ketogenesis enzymes. The reprogramming is impaired in circadian clock mutant mice. The circadian clock gated ketogenesis contributes to the diet impact on health and longevity.
2022-08-31 | GSE211975 | GEO
Project description:Recent evidence suggest that the circadian timing system plays an important role in the control of renal function and maintaining blood pressure. Here, we analyzed circadian rhythms of urinary excretion of sodium and potassium in wild-type mice and mice lacking circadian transcriptional activator clock. Analysis of urines collected at hourly intervals over a 24-hour period revealed dramatic changes in rhythms of sodium and potassium excretion in clock(-/-) mice. In parallel, significant differences in circadian pattern of plasma aldosterone levels, but not in the 24-hour mean aldosterone levels, were observed. Microarray-based profiling of renal transcriptomes demonstrated that clock(-/-) mice exhibit dysregulation in multiple mechanisms involved in maintaining sodium and potassium balance by the kidney. The most significant changes were detected in the expression levels of several key enzymes (Cyp4a14, Cyp4a12a and Cyp4a12b) required for the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a powerful regulator of renal sodium and potassium excretion, renal vascular tone and blood pressure. The 20-HETE levels measured in kidney microsomes of wild-type mice followed a circadian-like temporal pattern. In clock(-/-) mice, the acrophase of this rhythm was shifted by 8 hours and the 24-hour mean levels of 20-HETE were significantly decreased. These results demonstrate that circadian rhythms of urine electrolyte excretion are largely dependent on the circadian clock activity and indicate that circadian oscillations in renal 20-HETE content could be an important mechanism of blood pressure regulation. We examined the temporal profiles of gene expression in mouse whole kidney. Animals were sacrificed for microdissection every 4 hours, i.e. at ZT0, ZT4, ZT8, ZT12, ZT16 and ZT20 (ZT M-bM-^@M-^S Zeitgeber (circadian) time, indicates time of light-on as ZT0 and time of light-off as ZT12). The microarray hybridization was performed in duplicates on pools of RNA composed of equivalent amounts of RNA prepared from teo or three animals at each ZT time-point.
2012-04-29 | E-GEOD-27366 | biostudies-arrayexpress
Project description:The brain’s suprachiasmatic nucleus (SCN) is the master clock driving circadian rhythms in mammals. Vasoactive intestinal polypeptide (VIP) and its cognate receptor, VPAC2, are expressed in SCN neurons and mice with genetically targeted deletion of VPAC2 (Vipr2 -/-animals) show aberrant resetting to light, abnormal behavioral rhythms, and diminished SCN clock gene expression. Timed daily access to a running-wheel (scheduled voluntary exercise; SVE) promotes Vipr2 -/- SCN clock cell synchrony and 24h behavioral rhythms. We hypothesized that timed exercise alters the SCN transcriptome. Here, in control (Vipr2+/+) and Vipr2-/- mice under freely exercising and SVE conditions, RNAseq and qRT-PCR were used to measured gene expression of laser-dissected SCN. Compared to Vipr2+/+ mice, hundreds of genes were differentially expressed in the SCN from Vipr2-/- mice rhythmic in the freely exercising condition. Unexpectedly, SVE did not promote a Vipr2+/+-like SCN transcriptome in Vipr2-/- mice and many transcripts involved in SCN function including Avp, C1ql3, Gpr176, Prok2, Sst, Per2, and Nr1d1 remained dysregulated in the SVE condition. By contrast, circadian oscillators in the liver and lung were mostly intact in Vipr2-/- mice. This study indicates that marked molecular deficits in the SCN are sustained in behaviorally rhythmic Vipr2-/- mice, raising the possibility that a minimal functional SCN circadian clock can underpin whole animal rhythms.
2023-01-20 | GSE207992 | GEO