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MLL3/4 complex functions in ESCs. The MLL3/4 histone methyltransferases function as part of the COMPASS complex to promote H3K4 mono- and dimethylation (me1/2), using S-Adenosyl methionine (SAM) as a cofactor. In addition, MLL4 counteracts LSD1 to preserve H3K4me1. MLL3/4 also co-operate with P300 and UTX to promote H3K27 demethylation and acetylation (ac). Biologically, MLL3/4 proteins are required for exiting naïve pluripotency and proper differentiation into somatic lineages.
