Chromatin remodeling of histone H3 variants by DDM1 underlies epigenetic inheritance of DNA methylation

Lee, Seung Cho, Adams, Dexter W, Ipsaro, Jonathan J, Cahn, Jonathan, Lynn, Jason, Kim, Hyun-Soo, Berube, Benjamin, Major, Viktoria, Calarco, Joseph P, LeBlanc, Chantal, Bhattacharjee, Sonali, Ramu, Umamaheswari, Grimanelli, Daniel, Jacob, Yannick, Voigt, Philipp, Joshua-Tor, Leemor, Martienssen, Robert A (August 2023) Chromatin remodeling of histone H3 variants by DDM1 underlies epigenetic inheritance of DNA methylation. Cell, 186 (19). 4100-4116.e15. ISSN 0092-8674 (Public Dataset)

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Abstract

Nucleosomes block access to DNA methyltransferase, unless they are remodeled by DECREASE in DNA METHYLATION 1 (DDM1LSH/HELLS), a Snf2-like master regulator of epigenetic inheritance. We show that DDM1 promotes replacement of histone variant H3.3 by H3.1. In ddm1 mutants, DNA methylation is partly restored by loss of the H3.3 chaperone HIRA, while the H3.1 chaperone CAF-1 becomes essential. The single-particle cryo-EM structure at 3.2 Å of DDM1 with a variant nucleosome reveals engagement with histone H3.3 near residues required for assembly and with the unmodified H4 tail. An N-terminal autoinhibitory domain inhibits activity, while a disulfide bond in the helicase domain supports activity. DDM1 co-localizes with H3.1 and H3.3 during the cell cycle, and with the DNA methyltransferase MET1Dnmt1, but is blocked by H4K16 acetylation. The male germline H3.3 variant MGH3/HTR10 is resistant to remodeling by DDM1 and acts as a placeholder nucleosome in sperm cells for epigenetic inheritance.

Item Type:	Paper
Subjects:	organism description > plant > Arabidopsis bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA methylation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromatin remodeling bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > histone organism description > plant bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:	Ipsaro, Jonathan J. Berube, Benjamin Calarco, Joseph P. LeBlanc, Chantal Bhattacharjee, Sonali Ramu, Umamaheswari Jacob, Yannick Joshua-Tor, Leemor Martienssen, Robert A. Lee, Seung Cho Adams, Dexter Cahn, Jonathan Lynn, Jason Kim, Hyun Soo
Communities:	CSHL Cancer Center Program CSHL Cancer Center Program > Gene Regulation and Inheritance Program CSHL Cancer Center Shared Resources CSHL Cancer Center Shared Resources > Antibody and Phage Display Service CSHL labs > Joshua-Tor lab CSHL labs > Martienssen lab School of Biological Sciences > Publications
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	24 August 2023
Date Deposited:	21 Sep 2023 15:47
Last Modified:	29 Feb 2024 19:31
PMCID:	PMC10529913
Related URLs:	Publisher
Dataset ID:	GEO: GSE231563
URI:	https://repository.cshl.edu/id/eprint/40941

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