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

TY - JOUR

T1 - PRDM16 binds MED1 and controls chromatin architecture to determine a brown fat transcriptional program

AU - Harms, Matthew J

AU - Lim, Hee-Woong

AU - Ho, Yugong

AU - Shapira, Suzanne N

AU - Ishibashi, Jeff

AU - Rajakumari, Sona

AU - Steger, David J

AU - Lazar, Mitchell A

AU - Won, Kyoung-Jae

AU - Seale, Patrick

N1 - © 2015 Harms et al.; Published by Cold Spring Harbor Laboratory Press.

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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.

AB - 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.

KW - Adipose Tissue, Brown/metabolism

KW - Animals

KW - Chromatin/chemistry

KW - DNA-Binding Proteins/metabolism

KW - Enhancer Elements, Genetic

KW - Mediator Complex Subunit 1/metabolism

KW - Mice

KW - Transcription Factors/metabolism

KW - Transcription, Genetic/physiology

U2 - 10.1101/gad.252734.114

DO - 10.1101/gad.252734.114

M3 - Journal article

C2 - 25644604

SN - 0890-9369

VL - 29

SP - 298

EP - 307

JO - Genes & Development

JF - Genes & Development

IS - 3

ER -