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Genome-wide Circadian Control of Transcription at Active Enhancers Regulates Insulin Secretion and Diabetes Risk

ABSTRACT: The molecular clock is a transcriptional oscillator present in brain and peripheral cells that coordinates behavior and physiology with the solar cycle. Here we reveal that the clock gates insulin secretion through genome-wide transcriptional control of the pancreatic exocyst across species. Clock transcription factors bind to unique enhancer sites in cycling genes in beta cells that diverge from those in liver, revealing the dynamics of inter-tissue clock control of genomic and physiologic processes important in glucose homeostasis.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE69889 | GEO | 2015/11/10

SECONDARY ACCESSION(S): PRJNA287037

REPOSITORIES: GEO

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Genome-wide Circadian Control of Transcription at Active Enhancers Regulates Insulin Secretion and Diabetes Risk

Project description:The molecular clock is a transcriptional oscillator present in brain and peripheral cells that coordinates behavior and physiology with the solar cycle. Here we reveal that the clock gates insulin secretion through genome-wide transcriptional control of the pancreatic exocyst across species. Clock transcription factors bind to unique enhancer sites in cycling genes in beta cells that diverge from those in liver, revealing the dynamics of inter-tissue clock control of genomic and physiologic processes important in glucose homeostasis. Transcriptome profiling in mouse and human islets at serial 4-hour time intervals by polyA RNA-Seq

2015-11-10 | E-GEOD-69889 | biostudies-arrayexpress

Pancreatic Beta-Cell Enhancers Regulate Rhythmic Transcription of Exocyst Triggering and Diabetes [ChIP-seq]

2015-11-10 | E-GEOD-70960 | biostudies-arrayexpress

Pancreatic Beta-Cell Enhancers Regulate Rhythmic Transcription of Exocyst Triggering and Diabetes [ChIP-seq]

2015-11-10 | GSE70960 | GEO

Global Mapping at the Core of the Arabidopsis Circadian Clock Defines the Network Structure of the Oscillator

Project description:In many organisms, the circadian clock is composed of functionally coupled morning and evening oscillators that regulate the bouts of dawn and dusk activity. In Arabidopsis, oscillator coupling relies on a core loop in which the evening oscillator component TOC1 was proposed to activate a subset of morning-expressed oscillator genes. Our systems-biological approach overturns the current view of the Arabidopsis circadian clock showing that TOC1 does not function as an activator but as a timely-controlled general repressor of morning and evening oscillator components. Repression occurs through rhythmic binding to the promoters of all oscillator genes, suggesting a previously unexpected direct connection between the morning and evening loops.

2012-03-08 | GSE35952 | GEO

Clock controlled and cold induced CDF6 alters growth and development to changing temperatures

Project description:The circadian clock represents a critical regulatory network, which allows plants to anticipate environmental changes as inputs and promote plant survival by regulating various physiological outputs. Here, we examine the function of the clock-regulated transcription factor, CYCLING DOF FACTOR 6 (CDF6), during cold stress in Arabidopsis thaliana. We found that the clock gates CDF6 transcript accumulation in the vasculature during cold stress. CDF6 mis-expression results in an altered flowering phenotype during both ambient and cold stress. A genome-wide transcriptome analysis links CDF6 to genes associated with flowering and seed germination during cold and ambient temperatures, respectively. Analysis of key floral regulators indicates that CDF6 alters flowering during cold stress by repressing photoperiodic flowering components, FLOWERING LOCUS T (FT), CONSTANS (CO), and BROTHER OF FT (BFT). Gene ontology enrichment further suggests that CDF6 regulates circadian and developmental associated genes. These results provide insight into how the clock-controlled CDF6 modulates plant development during moderate cold stress.

2022-07-01 | GSE197581 | GEO

Global Mapping at the Core of the Arabidopsis Circadian Clock Defines the Network Structure of the Oscillator

2012-03-08 | E-GEOD-35952 | biostudies-arrayexpress

In vitro characterization of the human segmentation clock

Project description:The segmental organization of the vertebral column is established early in embryogenesis when pairs of somites are rhythmically produced by the presomitic mesoderm (PSM). The tempo of somite formation is controlled by a molecular oscillator known as the segmentation clock. While this oscillator has been well-characterized in model organisms, whether a similar oscillator exists in humans remains unknown. Genetic analysis of patients with severe spine segmentation defects have implicated several human orthologs of cyclic genes associated with the mouse segmentation clock, suggesting that this oscillator might be conserved in humans. Here we show that in vitro-derived human as well as mouse PSM cells recapitulate oscillations of the segmentation clock. Human PSM cells oscillate twice slower than mouse cells (5-hours vs. 2.5 hours), but are similarly regulated by FGF, Wnt, Notch and YAP. Single cell RNA-sequencing reveals that mouse and human PSM cells in vitro follow a similar developmental trajectory to mouse PSM in vivo. Furthermore, we demonstrate that FGF signaling controls the phase and period of oscillations, expanding the role of this pathway beyond its classical interpretation in 'Clock and Wavefront' models. Overall, our work identifying the human segmentation clock represents an important breakthrough for human developmental biology.

2019-10-28 | GSE114186 | GEO

MH003B:FOXO3 in control of circadian rhythms via direct regulation of Clock. Part 2: knockdown of FoxO3.

Project description:Circadian rhythms are responsive to a variety of external cues, light and metabolism being the most important. In mammals, the light signal is sensed by the retina and transmitted to the SCN master clock, where it is translated into the molecular oscillator via regulation of clock gene transcription. The signalling pathways governing the molecular translation from metabolic signals to circadian output in peripheral oscillators, in contrast, are less understood. FOXO transcription factors are known to translate external metabolic cues to internal transcriptional programs. In the past couple of years it has become evident that both FOXO transcription factors and the circadian clock are of key importance in the underlying mechanisms of ageing and the regulation of metabolism. We now show FOXO3 to be a crucial modulator of circadian rhythmicity via direct transcriptional regulation of Clock, a core component of the molecular oscillator, and identify FOXO3 as a novel link in the circadian feedback loop, which is required for circadian rhythms in liver. We propose that FOXO3 directly feeds back into the circadian oscillator in response to metabolic cues.

2014-06-03 | GSE41555 | GEO

MH003A:FOXO3 in control of circadian rhythms via direct regulation of Clock. Part 1: overexpression of FoxO6

2014-06-03 | GSE41554 | GEO

Murine hippocampal proteome - Phosphoproteome Profiling Reveals Circadian Clock Regulation of Posttranslational Modifications in the Murine Hippocampus

Project description:The circadian clock is an endogenous oscillator that drives daily rhythms in physiology, behavior and gene expression. The underlying mechanisms of circadian timekeeping are cell-autonomous and involve interconnecting transcription-translation feedback loops. The hippocampus plays an important role in spatial memory and the conversion of short-term to long-term memory. Several studies have reported the presence of a peripheral oscillator in the hippocampus, and have highlighted the importance of circadian regulation in memory formation. In this study we performed global quantitative proteome and phosphoproteome analyses of the murine hippocampus across the circadian cycle, applying spiked-in labeled reference and high accuracy mass spectrometry.

2017-04-11 | PXD005668 | Pride

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