Genomics

Dataset Information

299

Cistromic and epigenomic changes in Prdm16 knock-out brown adipose tissue


ABSTRACT: Prdm16 is a transcription factor that drives a complete program of brown adipocyte differentiation, but the mechanism by which Prdm16 activates gene transcription remains unknown. Utilizing ChIP-seq teqhnique, we found that Prdm16 binds to chromatin at/near many brown fat-selective genes in BAT. Interestingly, Prdm16-deficiency dramatically reduced the binding of Med1 to Prdm16-target sites. Indeed, Prdm16 binds and recruits Med1 to BAT-enriched genes and the loss of Prdm16 caused a fundamental change in chromatin architecture at key BAT-selective genes and also reduced transcirptional activity. Moreover, Prdm16, through its interaction with Med1, defines and regulates the activity of super-enhancers that drive the expression of cell identity genes. Together, these data demonstrate that Prdm16 drives gene transcription by recruiting Med1 to control chromatin architecture and super-enhancers. Brown adipose tissues were collected from Prdm16 knockout and wiletype 9-month-old mice and ChIP-seq was performed for Prdm16, PolII, Med1, and H3K27ac.

ORGANISM(S): Mus musculus  

SUBMITTER: Hee-Woong Lim   Jeff Ishibashi  Suzanne Shapira  Sona Rajakumari  Matthew J Harms  Yugong Ho  Kyoung-Jae Won  Patrick Seale 

PROVIDER: E-GEOD-63965 | ArrayExpress | 2015-02-10

SECONDARY ACCESSION(S): SRP050953GSE63965PRJNA269620

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

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]

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