Document Type
Journal Article
Publication Date
2017
Journal
Nature Communications
Inclusive Pages
2217
DOI
10.1038/s41467-017-02403-5
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Lee, J., Park, Y., Park, S., Jang, Y., Waring, N., Dey, A., Ozato, K., Lai, B., Peng, W., & Ge, K. (2017). Brd4 binds to active enhancers to control cell identity gene induction in adipogenesis and myogenesis. Nature Communications, (). http://dx.doi.org/10.1038/s41467-017-02403-5
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of Macmillan Publishers Ltd. Nature Communications