Peters Antoine H F M, Kubicek Stefan, Mechtler Karl, O'Sullivan Roderick J, Derijck Alwin A H A, Perez-Burgos Laura, Kohlmaier Alexander, Opravil Susanne, Tachibana Makoto, Shinkai Yoichi, Martens Joost H A, Jenuwein Thomas
Research Institute of Molecular Pathology, The Vienna Biocenter, Dr. Bohrgasse 7, A-1030 Vienna, Austria.
Mol Cell. 2003 Dec;12(6):1577-89. doi: 10.1016/s1097-2765(03)00477-5.
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.
组蛋白N端特定位置赖氨酸残基的甲基化是调控染色质表观遗传转变的核心修饰。每个可甲基化的赖氨酸残基可以以单甲基化、二甲基化或三甲基化状态存在，从而扩展了这种特定修饰的索引潜力。在此，我们研究了哺乳动物染色质中组蛋白H3赖氨酸9（H3-K9）和赖氨酸27（H3-K27）的所有可能甲基化状态。使用高度特异性抗体结合定量质谱分析，我们证明着丝粒周围异染色质选择性富集H3-K27单甲基化和H3-K9三甲基化。这种异染色质甲基化谱依赖于Suv39h组蛋白甲基转移酶（HMTases），但不依赖于常染色质的G9a HMTase。在Suv39h双敲除细胞中，着丝粒周围异染色质转变为其他甲基化印记，并积累H3-K27三甲基化和H3-K9单甲基化。我们的数据强调了在划分染色体亚结构域中不同组蛋白赖氨酸甲基化状态的选择性存在，但也揭示了真核染色质中甲基化模式传播的惊人可塑性。
