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Becht DC, Mohid SA, Lee JE, Zandian M, Benz C, Biswas S, Sinha VK, Ivarsson Y, Ge K, Zhang Y, Kutateladze TG
Structure 32 (6) 706-714.e3 [2024-06-06; online 2024-04-04]
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 of MLL4 (MLL4PHD6) binds to the hydrophobic motif of ten-eleven translocation 3 (TET3), a dioxygenase that converts methylated cytosine into oxidized derivatives. The solution NMR structure of the TET3-MLL4PHD6 complex and binding assays show that, like histone H4 tail, TET3 occupies the hydrophobic site of MLL4PHD6, and that this interaction is conserved in the seventh PHD finger of homologous MLL3 (MLL3PHD7). 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.
Bioinformatics Support for Computational Resources [Service]
NGI Stockholm (Genomics Production) [Service]
National Genomics Infrastructure [Service]
PubMed 38579707
DOI 10.1016/j.str.2024.03.005
Crossref 10.1016/j.str.2024.03.005
mid: NIHMS1979275
pmc: PMC11162309
pii: S0969-2126(24)00087-X