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

Science. 2014 Mar 14;343(6176):1249-53. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Arabidopsis / genetics
  • Arabidopsis / metabolism*
  • Arabidopsis Proteins / chemistry*
  • Arabidopsis Proteins / metabolism
  • Catalytic Domain
  • Conserved Sequence
  • Crystallography, X-Ray
  • DNA Replication
  • Epigenesis, Genetic
  • Gene Expression Regulation, Plant
  • Heterochromatin / metabolism*
  • Histones / metabolism*
  • Methylation
  • Methyltransferases / chemistry*
  • Methyltransferases / metabolism
  • Mitosis
  • Molecular Sequence Data
  • Protein Processing, Post-Translational*
  • Threonine / metabolism

Substances

  • Arabidopsis Proteins
  • Heterochromatin
  • Histones
  • Threonine
  • ATXR5 protein, Arabidopsis
  • ATXR6 protein, Arabidopsis
  • Methyltransferases

Associated data

  • PDB/4O30