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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.

SUBMITTER: Harms MJ

PROVIDER: S-EPMC4318146 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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PRDM16 binds MED1 and controls chromatin architecture to determine a brown fat transcriptional program.

Harms Matthew J MJ Lim Hee-Woong HW Ho Yugong Y Shapira Suzanne N SN Ishibashi Jeff J Rajakumari Sona S Steger David J DJ Lazar Mitchell A MA Won Kyoung-Jae KJ Seale Patrick P

Genes & development 20150201 3

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 ...[more]

PMID: 25644604

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