6MLC

PHD6 domain of MLL3 in complex with histone H4

Summary for 6MLC

• Entry DOI: 10.2210/pdb6mlc/pdb
• Descriptor: Histone-lysine N-methyltransferase 2C, Histone H4, ZINC ION, ... (6 entities in total)
• Functional Keywords: mll3, phd6, structural genomics, structural genomics consortium, sgc, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 47390.14

Authors

Dong, A.,Liu, Y.,Qin, S.,Lei, M.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Min, J.,Structural Genomics Consortium (SGC) (deposition date: 2018-09-27, release date: 2018-10-24, Last modification date: 2024-03-13)

Primary citation

Liu, Y.,Qin, S.,Chen, T.Y.,Lei, M.,Dhar, S.S.,Ho, J.C.,Dong, A.,Loppnau, P.,Li, Y.,Lee, M.G.,Min, J.
Structural insights into trans-histone regulation of H3K4 methylation by unique histone H4 binding of MLL3/4.
Nat Commun, 10:36-36, 2019

PubMed Abstract: MLL3 and MLL4 are two closely related members of the SET1/MLL family of histone H3K4 methyltransferases and are responsible for monomethylating histone H3K4 on enhancers, which are essential in regulating cell-type-specific gene expression. Mutations of MLL3 or MLL4 have been reported in different types of cancer. Recently, the PHD domains of MLL3/4 have been reported to recruit the MLL3/4 complexes to their target genes by binding to histone H4 during the NT2/D1 stem cell differentiation. Here we show that an extended PHD domain (ePHD) involving the sixth PHD domain and its preceding zinc finger in MLL3 and MLL4 specifically recognizes an H4H18-containing histone H4 fragment and that modifications of residues surrounding H4H18 modulate H4 binding to MLL3/4. Our in vitro methyltransferase assays and cellular experiments further reveal that the interaction between ePHD of MLL3/4 and histone H4 is required for their nucleosomal methylation activity and MLL4-mediated neuronal differentiation of NT2/D1 cells.

PubMed: 30604749
DOI: 10.1038/s41467-018-07906-3

Experimental method

X-RAY DIFFRACTION (1.8 Å)