MLL4 binds TET3

Human mixed lineage leukemia 4 (MLL4), also known as KMT2D, regulates cell type specific transcriptional programs through enhancer activation. Along with the catalytic methyltransferase domain, MLL4 contains seven less characterized plant homeodomain (PHD) fingers. Here, we report that the sixth PHD finger MLL4 (MLL4 PHD6 ) binds to the hydrophobic motif of ten -eleven translocation 3 (TET3), a dioxygenase converts methylated cytosine into oxidized derivatives. The solution NMR structure of the TET3-MLL4 complex and binding assays show that, like histone H4 tail, TET3 occupies the hydrophobic site MLL 4 PHD6 , and that this interaction is conserved in the seventh PHD finger of homologous MLL3 (MLL3 PHD7 Analysis of genomic localization of endogenous MLL4 and ectopically expressed TET3 in mouse embryonic stem cells reveals a high degree overlap on active enhancers and suggests a potential functional relationship of MLL4 and TET3.