title: PRDM16 binds MED1 and controls chromatin architecture to determine a brown fat transcriptional program.
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.
authors: Institute for Diabetes, Obesity, and Metabolism, Department of Cell and Developmental Biology.
authors: Matthew J
authors: MJ
authors: Harms
authors: Institute for Diabetes, Obesity, and Metabolism, Genetics Department, Smilow Center for Translational Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors: Hee-Woong
authors: HW
authors: Lim
authors: Genetics Department, Smilow Center for Translational Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA sealep@upenn.edu wonk@upenn.edu.
authors: Yugong
authors: Y
authors: Ho
authors: Institute for Diabetes, Obesity, and Metabolism, Department of Cell and Developmental Biology.
authors: Suzanne N
authors: SN
authors: Shapira
authors: Institute for Diabetes, Obesity, and Metabolism, Department of Cell and Developmental Biology.
authors: Jeff
authors: J
authors: Ishibashi
authors: Institute for Diabetes, Obesity, and Metabolism, Department of Cell and Developmental Biology.
authors: Sona
authors: S
authors: Rajakumari
authors: Institute for Diabetes, Obesity, and Metabolism.
authors: David J
authors: DJ
authors: Steger
authors: Institute for Diabetes, Obesity, and Metabolism.
authors: Mitchell A
authors: MA
authors: Lazar
authors: Institute for Diabetes, Obesity, and Metabolism, Genetics Department, Smilow Center for Translational Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors: Kyoung-Jae
authors: KJ
authors: Won
authors: Institute for Diabetes, Obesity, and Metabolism, Department of Cell and Developmental Biology, sealep@upenn.edu wonk@upenn.edu.
authors: Patrick
authors: P
authors: Seale
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D056913:Mediator Complex Subunit 1 / Q000378:metabolism*; D051379:Mice; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; C538856:Med1 protein, mouse; D056913:Mediator Complex Subunit 1; C521133:Prdm16 protein, mouse; D014157:Transcription Factors
keywords: MED1; Mediator; PRDM16; PRDM3; UCP1; brown adipose tissue
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