@article{ea4cca6820e747a1a0dfd1453b51c304,
title = "SRC-2 Is an Essential Coactivator for Orchestrating Metabolism and Circadian Rhythm",
abstract = "Synchrony of the mammalian circadian clock is achieved by complex transcriptional and translational feedback loops centered on the BMAL1:CLOCK heterodimer. Modulation of circadian feedback loops is essential for maintaining rhythmicity, yet the role of transcriptional coactivators in driving BMAL1:CLOCK transcriptional networks is largely unexplored. Here, we show diurnal hepatic steroid receptor coactivator 2 (SRC-2) recruitment to the genome that extensively overlaps with the BMAL1 cistrome during the light phase, targetinggenes that enrich for circadian and metabolic processes. Notably, SRC-2 ablation impairs wheel-running behavior, alters circadian gene expression in several peripheral tissues, alters the rhythmicity of the hepatic metabolome, and deregulates the synchronization of cell-autonomous metabolites. We identify SRC-2 as a potent coregulator of BMAL1:CLOCK and find that SRC-2 targets itself with BMAL1:CLOCK in a feedforward loop. Collectively, our data suggest that SRC-2 is a transcriptional coactivator of the BMAL1:CLOCK oscillators and establish SRC-2 as a critical positive regulator of the mammalian circadian clock.",
author = "Erin Stashi and Lanz, {Rainer B.} and Jianqiang Mao and George Michailidis and Bokai Zhu and Kettner, {Nicole M.} and Nagireddy Putluri and Reineke, {Erin L.} and Reineke, {Lucas C.} and Subhamoy Dasgupta and Adam Dean and Stevenson, {Connor R.} and Natarajan Sivasubramanian and Arun Sreekumar and Francesco DeMayo and Brian York and Loning Fu and O'Malley, {Bert W.}",
note = "Funding Information: We thank C. Ljungberg and staff at the IDDRC RNA In Situ Hybridization Core for performing all in situ hybridization staining, supported by BCM IDDRC grant 5P30HD024064-23 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. We thank the MMRU staff for performing measurements of food intake in the Mouse Metabolic Research Unit at the USDA/ARS Children{\textquoteright}s Nutrition Research Center, supported by funds from the USDA ARS ( https://www.bcm.edu/cnrc/mmru ). We would also like to thank V. Putluri for her help with the metabolic phenotype microarray. This research was supported by grants from the NIH (NCI F31CA171350 to E.S., NIDDK PO1 P01 DK59820, and 3U19DK062434-10W1 to B.W.O{\textquoteright}M.) and the Welch Foundation (Q1521). Additionally, funding support was provided from the Center for the Advancement of Science in Space (CASIS) Integrated OMICs Award (to B.Y., R.B.L., A.S., and B.W.O.). Partial funding support was provided by NIH grants R01 CA137019-01A (to L.F.) and P01 DK59820, CPRIT RP120092 (to A.S. and N.P.), and the Genetically Engineered Mouse Shared Resources with F. DeMayo. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Eunice Kennedy Shriver National Institute of Child Health and Human Development. ",
year = "2014",
doi = "10.1016/j.celrep.2014.01.027",
language = "English (US)",
volume = "6",
pages = "633--645",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}