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| Status |
Public on Nov 17, 2017 |
| Title |
Enhancer-binding of Brd4 controls cell differentiation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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.
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| 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
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| Contributor(s) |
Lee J, Park Y, Park S, Jang Y, Waring N, Lai B, Peng W, Ge K |
| Citation(s) |
29263365 |
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| Submission date |
May 19, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Kai Ge |
| E-mail(s) |
kai.ge@nih.gov
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| Phone |
301-451-1998
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| Organization name |
NIH
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| Department |
NIDDK
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| Street address |
50 South Dr Rm 4154
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (34)
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| Relations |
| BioProject |
PRJNA387297 |
| SRA |
SRP107492 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE99101_RAW.tar |
121.5 Mb |
(http)(custom) |
TAR (of TXT, WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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