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Unknown,Transcriptomics,Genomics,Proteomics

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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. Transcriptome profiling in mouse and human islets at serial 4-hour time intervals by polyA RNA-Seq

ORGANISM(S): Mus musculus

SUBMITTER: Mark Perelis

PROVIDER: E-GEOD-69889 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Pancreatic β cell enhancers regulate rhythmic transcription of genes controlling insulin secretion.

Perelis Mark M Marcheva Biliana B Ramsey Kathryn Moynihan KM Schipma Matthew J MJ Hutchison Alan L AL Taguchi Akihiko A Peek Clara Bien CB Hong Heekyung H Huang Wenyu W Omura Chiaki C Allred Amanda L AL Bradfield Christopher A CA Dinner Aaron R AR Barish Grant D GD Bass Joseph J

Science (New York, N.Y.) 20151101 6261

The mammalian transcription factors CLOCK and BMAL1 are essential components of the molecular clock that coordinate behavior and metabolism with the solar cycle. Genetic or environmental perturbation of circadian cycles contributes to metabolic disorders including type 2 diabetes. To study the impact of the cell-autonomous clock on pancreatic β cell function, we examined pancreatic islets from mice with either intact or disrupted BMAL1 expression both throughout life and limited to adulthood. We ...[more]

PMID: 26542580

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Pancreatic Beta Cell Enhancers Regulate Rhythmic Transcription of Exocyst Triggering and Diabetes

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Mouse SCN in LC-MSMS - The suprachiasmatic nucleus (SCN) acts as the central clock to coordinate circadian oscillations in mammalian behavior, physiology and gene expression. Despite our knowledge of the circadian transcriptome of the SCN, how it impacts genome-wide protein expression is not well understood. Here, we interrogated the murine SCN proteome across the circadian cycle using SILAC-based quantitative mass spectrometry.

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