title: Selective methylation of histone H3 variant H3.1 regulates heterochromatin replication.
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.
authors.affiliation: Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Jacob
authors.forename: Elisa
authors.initials: E
authors.lastname: Bergamin
authors.forename: Mark T A
authors.initials: MT
authors.lastname: Donoghue
authors.forename: Vanessa
authors.initials: V
authors.lastname: Mongeon
authors.forename: Chantal
authors.initials: C
authors.lastname: LeBlanc
authors.forename: Philipp
authors.initials: P
authors.lastname: Voigt
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Underwood
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Brunzelle
authors.forename: Scott D
authors.initials: SD
authors.lastname: Michaels
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Couture
authors.forename: Robert A
authors.initials: RA
authors.lastname: Martienssen
mesh_terms: D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism*; D029681:Arabidopsis Proteins / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004261:DNA Replication; D044127:Epigenesis, Genetic; D018506:Gene Expression Regulation, Plant; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000737:chemistry* / Q000378:metabolism; D008938:Mitosis; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D013912:Threonine / Q000378:metabolism
chemical_list: D029681:Arabidopsis Proteins; D006570:Heterochromatin; D006657:Histones; D013912:Threonine; C542364:ATXR5 protein, Arabidopsis; C542365:ATXR6 protein, Arabidopsis; D008780:Methyltransferases