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Title: Family-wide Characterization of Histone Binding Abilities of Human CW Domain-containing Proteins

Journal Article · · Journal of Biological Chemistry
 [1];  [2];  [2];  [3];  [2];  [4];  [1]
  1. Univ. of Toronto, ON (Canada); Central China Normal Univ., Wuhan (China)
  2. Univ. of Toronto, ON (Canada)
  3. Central China Normal Univ., Wuhan (China)
  4. Univ. of Toronto, ON (Canada); South Univ. of Science and Technology of China, Shenzhen (China)
+ Show Author Affiliations

Covalent modifications of histone N-terminal tails play a critical role in regulating chromatin structure and controlling gene expression. These modifications are controlled by histone-modifying enzymes and read out by histone-binding proteins. Numerous proteins have been identified as histone modification readers. Here we report the family-wide characterization of histone binding abilities of human CW domain-containing proteins. We demonstrate that the CW domains in ZCWPW2 and MORC3/4 selectively recognize histone H3 trimethylated at Lys-4, similar to ZCWPW1 reported previously, while the MORC1/2 and LSD2 lack histone H3 Lys-4 binding ability. Our crystal structures of the CW domains of ZCWPW2 and MORC3 in complex with the histone H3 trimethylated at Lys-4 peptide reveal the molecular basis of this interaction. In each complex, two tryptophan residues in the CW domain form the “floor” and “right wall,” respectively, of the methyllysine recognition cage. Our mutation results based on ZCWPW2 reveal that the right wall tryptophan residue is essential for binding, and the floor tryptophan residue enhances binding affinity. Here, our structural and mutational analysis highlights the conserved roles of the cage residues of CW domain across the histone methyllysine binders but also suggests why some CW domains lack histone binding ability.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Natural Science Foundation of China (NSFC)
Grant/Contract Number:
AC02-06CH11357; 31500613; 092809/Z/10/Z
OSTI ID:
1254511
Journal Information:
Journal of Biological Chemistry, Vol. 291, Issue 17; ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular BiologyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 41 works
Citation information provided by
Web of Science

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Cited By (13)

Family-Wide Characterization of Histone Binding Abilities of PHD Domains of AL Proteins in Arabidopsis thaliana journal September 2018
Structure and mechanism of plant histone mark readers journal October 2017
Hyperactivation of HUSH complex function by Charcot–Marie–Tooth disease mutation in MORC2 journal June 2017
Structural insights into trans-histone regulation of H3K4 methylation by unique histone H4 binding of MLL3/4 journal January 2019
Mechanism for autoinhibition and activation of the MORC3 ATPase journal March 2019
Uncovering the mechanistic basis for specific recognition of monomethylated H3K4 by the CW domain of Arabidopsis histone methyltransferase SDG8 journal March 2018
Structural insight into inhibitors of flavin adenine dinucleotide-dependent lysine demethylases journal February 2017
ZCWPW1 is recruited to recombination hotspots by PRDM9, and is essential for meiotic double strand break repair posted_content October 2019
The histone modification reader ZCWPW1 links histone methylation to repair of PRDM9-induced meiotic double stand breaks posted_content May 2020
Wide Grain 7 increases grain width by enhancing H3K4me3 enrichment in the OsMADS1 promoter in rice ( Oryza sativa L.) journal January 2020
Neuropathic MORC2 mutations perturb GHKL ATPase dimerization dynamics and epigenetic silencing by multiple structural mechanisms text January 2018
Neuropathic MORC2 mutations perturb GHKL ATPase dimerization dynamics and epigenetic silencing by multiple structural mechanisms journal February 2018
Hyperactivation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2 text January 2017

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Related Subjects

60 APPLIED LIFE SCIENCES
chromatin structure
histone methylation
histone modification
post-translational modification (PTM)
protein-protein interaction
CW domain
H3K4 methylation
MORC3
ZCWPW2