Genomics

Dataset Information

302

Discrete Functions of Rev-erba Couple Metabolism to the Clock [HTS]


ABSTRACT: Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erb , a transcription factor (TF) that functions both as a core repressive component of the cell autonomous clock and as a regulator of metabolic genes. Here we show that Rev-erb modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erb to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erb regulates metabolic genes primarily by recruiting the HDAC3 corepressor to sites to which it is tethered by cell type-specific transcription factors. Thus, direct competition between Rev-erb and ROR TFs provides a universal mechanism for self-sustained control of molecular clock across all tissues, whereas Rev-erb utilizes lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue. Biological replicates were uploaded in separated files and indicated in the file names.

ORGANISM(S): Mus musculus  

SUBMITTER: Jennifer Jager   Dan Feng  Raymond E Soccio  Zheng Sun  Mitchell A Lazar  Jarrett R Remsberg  Bin Fang  Matthew J Emmett  Sean M Armour  Yuxiang Zhang  Manashree Damle  David J Steger 

PROVIDER: E-GEOD-67962 | ArrayExpress | 2015-06-16

SECONDARY ACCESSION(S): GSE67962SRP057271PRJNA281384

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

GENE REGULATION. Discrete functions of nuclear receptor Rev-erbα couple metabolism to the clock.

Zhang Yuxiang Y   Fang Bin B   Emmett Matthew J MJ   Damle Manashree M   Sun Zheng Z   Feng Dan D   Armour Sean M SM   Remsberg Jarrett R JR   Jager Jennifer J   Soccio Raymond E RE   Steger David J DJ   Lazar Mitchell A MA  

Science (New York, N.Y.) 20150604 6242


Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erbα, a transcription factor (TF) that functions both as a core repressive component of the cell-autonomous clock and as a regulator of metabolic genes. Here, we show that Rev-erbα modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erbα to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erbα regulates metab  ...[more]

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