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

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

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Enhancers play a central role in cell-type-specific gene expression and are marked by H3K4me1/2.Active enhancers are further argan oil pure purple 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, bekindtopets.com these findings identify MLL4 as a major mammalian H3K4 mono- and di-methyltransferase essential for enhancer activation during cell differentiation.