Enhancers control cell type-specific gene expression and direct cell fate transition. Enhancers are marked by H3K4me1/2. MLL4 (KMT2D) is a major enhancer H3K4me1/2 methyltransferase. Here we show in embryonic stem cells (ESCs), MLL4 associates with, but is dispensable for the maintenance of, active enhancers of ESC identity genes. As a result, MLL4 is dispensable for cell identity gene expression and self-renewal in ESCs. In contrast, MLL4 is essential for activation of de novo enhancers and induction of cell identity genes during ESC differentiation. Similarly, MLL4 is dispensable for maintaining fibroblast cell identity but is essential for reprogramming into induced pluripotent stem cells. These results indicate that while MLL4 is dispensable for maintaining cell identity, it controls cell fate transitions by orchestrating de novo enhancer activation. SOURCE: Kai Ge (kai.ge@nih.gov) -  NIH

Pluto Bioinformatics

GSE50534: Function of MLL4 in mouse embryonic stem cells and somatic cell reprogramming