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 (ePHD6) 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 ePHD6 of MLL3/4 and histone H4 is required for their nucleosomal methylation activity and MLL4-mediated neuronal differentiation of NT2/D1 cells.

Details

Title
Structural insights into trans-histone regulation of H3K4 methylation by unique histone H4 binding of MLL3/4
Author
Liu, Yanli 1 ; Su, Qin 1 ; Tsai-Yu, Chen 2 ; Lei, Ming 1 ; Dhar, Shilpa S 2 ; Jolene Caifeng Ho 1 ; Dong, Aiping 1 ; Loppnau, Peter 1 ; Li, Yanjun 1   VIAFID ORCID Logo  ; Lee, Min Gyu 2 ; Min, Jinrong 3 

1  Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada 
2  Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, USA 
3  Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada 
Pages
1-11
Publication year
2019
Publication date
Jan 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-07906-3
ProQuest document ID
2163007756
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.