NDLI: H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation

Content Provider	PubMed Central
Author	Lee, Ji-eun Wang, Chaochen Xu, Shiliyang Cho, Young-wook Wang, Lifeng Feng, Xuesong Baldridge, Anne Sartorelli, Vittorio Zhuang, Lenan Peng, Weiqun Ge, Kai
Editor	Glass, Christopher
Copyright Year	2013
Abstract	Enhancers play a central role in cell-type-specific gene expression and are marked by H3K4me1/2. Active enhancers are further marked by H3K27ac. However, the methyltransferases responsible for H3K4me1/2 on enhancers remain elusive. Furthermore, how these enzymes function on enhancers to regulate cell-type-specific gene expression is unclear. In this study, we identify MLL4 (KMT2D) as a major mammalian H3K4 mono- and di-methyltransferase with partial functional redundancy with MLL3 (KMT2C). Using adipogenesis and myogenesis as model systems, we show that MLL4 exhibits cell-type- and differentiation-stage-specific genomic binding and is predominantly localized on enhancers. MLL4 co-localizes with lineage-determining transcription factors (TFs) on active enhancers during differentiation. Deletion of Mll4 markedly decreases H3K4me1/2, H3K27ac, Mediator and Polymerase II levels on enhancers and leads to severe defects in cell-type-specific gene expression and cell differentiation. Together, these findings identify MLL4 as a major mammalian H3K4 mono- and di-methyltransferase essential for enhancer activation during cell differentiation.
Related Links	http://dx.doi.org/10.7554/elife.01503
Starting Page	1503
File Format	PDF
ISSN	2050084X
e-ISSN	2050084X
Journal	eLife
Volume Number	2
Language	English
Publisher	eLife Sciences Publications, Ltd
Publisher Date	2013-12-01
Access Restriction	Open
Rights Holder	eLife Sciences Publications, Ltd
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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