PRDM16 binds MED1 and controls chromatin architecture to determine a brown fat transcriptional program
- Matthew J. Harms1,2,4,
- Hee-Woong Lim1,3,4,
- Yugong Ho3,
- Suzanne N. Shapira1,2,
- Jeff Ishibashi1,2,
- Sona Rajakumari1,2,
- David J. Steger1,
- Mitchell A. Lazar1,
- Kyoung-Jae Won1,3 and
- Patrick Seale1,2
- 1Institute for Diabetes, Obesity, and Metabolism,
- 2Department of Cell and Developmental Biology,
- 3Genetics Department, Smilow Center for Translational Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
- Corresponding author: sealep{at}upenn.edu, wonk{at}upenn.edu
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↵4 These authors contributed equally to this work.
Abstract
PR (PRD1–BF1–RIZ1 homologous) domain-containing 16 (PRDM16) drives a brown fat differentiation program, but the mechanisms by which PRDM16 activates brown fat-selective genes have been unclear. Through chromatin immunoprecipitation (ChIP) followed by deep sequencing (ChIP-seq) analyses in brown adipose tissue (BAT), we reveal that PRDM16 binding is highly enriched at a broad set of brown fat-selective genes. Importantly, we found that PRDM16 physically binds to MED1, a component of the Mediator complex, and recruits it to superenhancers at brown fat-selective genes. PRDM16 deficiency in BAT reduces MED1 binding at PRDM16 target sites and causes a fundamental change in chromatin architecture at key brown fat-selective genes. Together, these data indicate that PRDM16 controls chromatin architecture and superenhancer activity in BAT.
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Footnotes
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.252734.114.
- Received September 17, 2014.
- Accepted December 10, 2014.
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