8U2Y

Solution structure of the PHD6 finger of MLL4 bound to TET3

Summary for 8U2Y

• Entry DOI: 10.2210/pdb8u2y/pdb
• NMR Information: BMRB: 31105
• Descriptor: Methylcytosine dioxygenase TET3, Histone-lysine N-methyltransferase 2D, ZINC ION (3 entities in total)
• Functional Keywords: kmt2d, tet3, chromatin, epigenetics, gene regulation
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 7822.44

Authors

Mohid, S.A.,Zandian, M.,Zhang, Y.,Kutateladze, T.G. (deposition date: 2023-09-06, release date: 2024-06-19)

Primary citation

Becht, D.C.,Mohid, S.A.,Lee, J.E.,Zandian, M.,Benz, C.,Biswas, S.,Sinha, V.K.,Ivarsson, Y.,Ge, K.,Zhang, Y.,Kutateladze, T.G.
MLL4 binds TET3.
Structure, 32:706-714.e3, 2024

PubMed Abstract: 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 (MLL4) 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-MLL4 complex and binding assays show that, like histone H4 tail, TET3 occupies the hydrophobic site of MLL4, and that this interaction is conserved in the seventh PHD finger of homologous MLL3 (MLL3). 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.

PubMed: 38579707
DOI: 10.1016/j.str.2024.03.005

Experimental method

SOLUTION NMR