October 9 - 12, 2012
Building 10 & Natcher Conference Center
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- Opening Plenary Session
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- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
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H3K4 mono-/di-methyltransferase MLL4 marks adipogenic enhancers and controls adipocyte differentiation
| Friday, November 08, 2013 — Poster Session III | |||
|---|---|---|---|
10:00 a.m. – 12:00 p.m. |
FAES Academic Center (Upper-Level Terrace) |
NIDDK |
CHROM-3 |
Authors
- J. Lee
- C. Wang
- S. Xu
- W. Peng
- K. Ge
Abstract
Spatiotemporal regulation of transcription is critical for animal development. Enhancer is an essential regulatory element that controls tissue- and stage-specific gene expression. Recent genome-wide association studies indicate that enhancers are marked by high levels of H3K4me1/2. Active enhancers are further marked by H3K27ac. However, several questions remain open. First, which methyltransferases are responsible for H3K4me1/2 on enhancers? Second, how are these methyltransferases recruited to enhancers? Third, what is the functional significance of H3K4me1/2? We previously purified the MLL3/MLL4-containing H3K4 methyltransferase complex. We further showed that PTIP, a component of MLL3/MLL4 complex, is critical for adipogenesis. Here we show that MLL4 is a major H3K4 mono-/di-methyltrasferase, and that MLL4 directly controls the induction of adipogenesis genes. Genome-wide profiling reveals extensive co-localization of MLL4 with master adipogenic transcription factors C/EBPs and PPARgamma on enhancers. Further, deletion of MLL4 leads to decreases of H3K4me1/2 and H3K27ac on enhancers, indicating that MLL4 is the dominant H3K4 mono/di-methyltransferase required for enhancer activation. Finally, overexpression of C/EBPbeta alone markedly increases MLL4-mediated H3K4me1 on enhancers, suggesting that C/EBPbeta recruits MLL4 to establish enhancer chromatin signature. Together, our data suggest that the master transcription factors recruit H3K4 mono-/di-methyltransferase MLL4 to establish and activate enhancers critical for cell differentiation.
