Partitioning and Plasticity of Repressive Histone Methylation States in Mammalian Chromatin

Antoine H.F.M. Peters, Stefan Kubicek, Karl Mechtler, Roderick J. O'Sullivan, Alwin A.H.A. Derijck, Laura Perez-Burgos, Alexander Kohlmaier, Susanne Opravil, Makoto Tachibana, Yoichi Shinkai, Joost H.A. Martens, Thomas Jenuwein

Research output: Contribution to journalArticleAcademicpeer-review

928 Citations (Scopus)

Abstract

Methylation of position-specific lysine residues in histone N termini is a central modification for regulating epigenetic transitions in chromatin. Each methylatable lysine residue can exist in a mono-, di-, or trimethylated state, thereby extending the indexing potential of this particular modification. Here, we examine all possible methylation states for histone H3 lysine 9 (H3-K9) and lysine 27 (H3-K27) in mammalian chromatin. Using highly specific antibodies together with quantitative mass spectrometry, we demonstrate that pericentric heterochromatin is selectively enriched for H3-K27 monomethylation and H3-K9 trimethylation. This heterochromatic methylation profile is dependent on the Suv39h histone methyltransferases (HMTases) but independent of the euchromatic G9a HMTase. In Suv39h double null cells, pericentric heterochromatin is converted to alternative methylation imprints and accumulates H3-K27 trimethylation and H3-K9 monomethylation. Our data underscore the selective presence of distinct histone lysine methylation states in partitioning chromosomal subdomains but also reveal a surprising plasticity in propagating methylation patterns in eukaryotic chromatin.

Original languageEnglish
Pages (from-to)1577-1589
Number of pages13
JournalMolecular Cell
Volume12
Issue number6
DOIs
Publication statusPublished - Dec 2003

Cite this