Selective methylation of histone H3 variant H3.1 regulates heterochromatin replication

Jacob, Y., Bergamin, E., Donoghue, M. T., Mongeon, V., LeBlanc, C., Voigt, P., Underwood, C. J., Brunzelle, J. S., Michaels, S. D., Reinberg, D., Couture, J. F., Martienssen, R. A. (March 2014) Selective methylation of histone H3 variant H3.1 regulates heterochromatin replication. Science, 343 (6176). pp. 1249-53. ISSN 0036-8075

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URL: http://www.ncbi.nlm.nih.gov/pubmed/24626927

DOI: 10.1126/science.1248357

Abstract

Histone variants have been proposed to act as determinants for posttranslational modifications with widespread regulatory functions. We identify a histone-modifying enzyme that selectively methylates the replication-dependent histone H3 variant H3.1. The crystal structure of the SET domain of the histone H3 lysine-27 (H3K27) methyltransferase ARABIDOPSIS TRITHORAX-RELATED PROTEIN 5 (ATXR5) in complex with a H3.1 peptide shows that ATXR5 contains a bipartite catalytic domain that specifically "reads" alanine-31 of H3.1. Variation at position 31 between H3.1 and replication-independent H3.3 is conserved in plants and animals, and threonine-31 in H3.3 is responsible for inhibiting the activity of ATXR5 and its paralog, ATXR6. Our results suggest a simple model for the mitotic inheritance of the heterochromatic mark H3K27me1 and the protection of H3.3-enriched genes against heterochromatization during DNA replication.

Item Type:	Paper
Uncontrolled Keywords:	Amino Acid Sequence Arabidopsis/genetics/metabolism Arabidopsis Proteins/chemistry/metabolism Catalytic Domain Conserved Sequence Crystallography, X-Ray DNA Replication Epigenesis, Genetic Gene Expression Regulation, Plant Heterochromatin/metabolism Histones/metabolism Methylation Methyltransferases/chemistry/metabolism Mitosis Molecular Sequence Data Protein Processing, Post-Translational Threonine/metabolism
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics > heterochromatin bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > histone bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein methylation > histone methylation
CSHL Authors:	Donoghue, Mark Jacob, Yannick Martienssen, Robert A. LeBlanc, Chantal Underwood, Charles
Communities:	CSHL labs > Martienssen lab School of Biological Sciences > Publications CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
Depositing User:	Matt Covey
Date:	14 March 2014
Date Deposited:	28 Mar 2014 19:32
Last Modified:	16 Jul 2021 19:46
PMCID:	PMC4049228
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/29730

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