1. H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation
- Author
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Lee, Ji-Eun, Wang, Chaochen, Xu, Shiliyang, Cho, Young-Wook, Wang, Lifeng, Feng, Xuesong, Sartorelli, Vittorio, Baldridge, Anne, Peng, Weiqun, and Ge, Kai
- Subjects
Quantitative Biology - Genomics - 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. Here 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, Polymerase II and Mediator 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., Comment: eLife 2013
- Published
- 2013