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| Status |
Public on Jan 01, 2017 |
| Title |
MLL3/MLL4 are required for CBP/p300 binding on enhancers and super-enhancer formation in brown adipogenesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Histone H3K4me1/2 methyltransferases MLL3/MLL4 and H3K27 acetyltransferases CBP/p300 are major enhancer epigenomic writers. To understand how these epigenomic writers orchestrate enhancer landscapes during cell differentiation, we have profiled genomic binding of MLL4, CBP, lineage-determining transcription factors, as well as transcriptome and epigenome during adipogenesis of immortalized preadipocytes derived from mouse brown adipose tissue (BAT). We show that MLL4 and CBP drive the dynamic enhancer epigenome, which correlates with the dynamic transcriptome. MLL3/MLL4 are required for CBP/p300 binding on enhancers activated during adipogenesis. Further, we show that MLL4 and CBP identify super-enhancers of adipogenesis and that MLL3/MLL4 are required for the formation of super-enhancers. Finally, in brown adipocytes differentiated in culture, MLL4 identifies primed super-enhancers of genes fully activated in BAT such as the thermogenic Ucp1. Comparison of MLL4-defined super-enhancers in brown and white adipogenesis predicted a list of brown-specific super-enhancers SEs associated genes that are likely to be important to BAT functions. These results establish MLL3/MLL4 and CBP/p300 as master enhancer epigenomic writers and suggest that enhancer-priming by MLL3/MLL4 followed by enhancer-activation by CBP/p300 sequentially shape dynamic enhancer landscapes during cell differentiation. Our data also provide a rich resource for understanding epigenomic regulation of brown adipogenesis.
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| Overall design |
Expression profiling by RNA-seq, profiling of transcription factors (EBF2, C/EBPβ, C/EBPα, PPARγ, and CTCF) binding, co-factors (MLL4, CBP, and Med1) and Pol II localization, and histone modifications (H3K4me1/2/3, H3K27ac, H3K36me3, H3K9me2, and H3K27me3) by ChIP-seq, and chromatin accessibility profiling by FAIRE-seq at four time points (D-3, D0, D2, D7) during adipogenesis of Ppargf/f brown preadipocytes in culture. ChIP-seq of CBP/p300 are performed at day2 of adipogenesis of Mll3-/-;Mll4f/f and Mll3-/-;Mll4-/- mouse brown preadipocytes in culture. In addition, ChIP-Seq of MLL4 are performed at day7 of aidpogenesis of 3T3L1 preadipocytes in culture.
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| Contributor(s) |
Binbin L, Ji-Eun L, Lifeng W, Younghoon J, Weiqun P, Kai G |
| Citation(s) |
28398509 |
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| Submission date |
Oct 20, 2015 |
| Last update date |
May 15, 2019 |
| 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 (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (89)
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| Relations |
| BioProject |
PRJNA299295 |
| SRA |
SRP065028 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE74189_RAW.tar |
537.8 Mb |
(http)(custom) |
TAR (of BED, TXT, WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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