Genomics

Dataset Information

157

Enhancer-binding of Brd4 controls cell differentiation


ABSTRACT: The epigenomic reader Brd4 is an important drug target for cancers. However, its role in cell differentiation and animal development remains largely unclear. Using two conditional knockout mouse strains and derived cells, we demonstrate that Brd4 controls cell identity gene induction and is essential for adipogenesis and myogenesis. Brd4 co-localizes with lineage-determining transcription factors (LDTFs) on active enhancers during differentiation. LDTFs coordinate with H3K4 mono-methyltransferases MLL3/MLL4 (KMT2C/KMT2D) and H3K27 acetyltransferases CBP/p300 to recruit Brd4 to enhancers activated during differentiation. Brd4 deletion prevents the enrichment of Mediator and RNA polymerase II transcription machinery, but not that of LDTFs, MLL3/MLL4-mediated H3K4me1, and CBP/p300-mediated H3K27ac, on enhancers. Consequently, Brd4 deletion prevents enhancer RNA production, cell identity gene induction and cell differentiation. Interestingly, Brd4 is dispensable for maintaining cell identity genes in differentiated cells. These findings identify Brd4 as an enhancer epigenomic reader that links active enhancers with cell identity gene induction in differentiation. Overall design: Expression profiling by RNA-seq, and profiling of Brd4 by ChIP-seq during adipogenesis of brown preadipocytes in culture (D0, D2, D7) and in C2C12 myocytes

INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)

SUBMITTER: Kai Ge  

PROVIDER: GSE99101 | GEO | 2017-11-17

SECONDARY ACCESSION(S): PRJNA387297

REPOSITORIES: GEO

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Publications

Brd4 binds to active enhancers to control cell identity gene induction in adipogenesis and myogenesis.

Lee Ji-Eun JE   Park Young-Kwon YK   Park Sarah S   Jang Younghoon Y   Waring Nicholas N   Dey Anup A   Ozato Keiko K   Lai Binbin B   Peng Weiqun W   Ge Kai K  

Nature communications 20171220 1


The epigenomic reader Brd4 is an important drug target for cancers. However, its role in cell differentiation and animal development remains largely unclear. Using two conditional knockout mouse strains and derived cells, we demonstrate that Brd4 controls cell identity gene induction and is essential for adipogenesis and myogenesis. Brd4 co-localizes with lineage-determining transcription factors (LDTFs) on active enhancers during differentiation. LDTFs coordinate with H3K4 mono-methyltransferas  ...[more]

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