Max-Planck-Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Nat Commun. 2013;4:2233. doi: 10.1038/ncomms3233.
To ensure genome stability, pericentromeric regions are compacted in a dense heterochromatic structure through a combination of specific 'epigenetic' factors and modifications. A cascadal pathway is responsible for establishing pericentromeric chromatin involving chromatin modifiers and 'readers', such as H3K9 histone methyltransferases (Suv)39h and heterochromatin protein 1. Here we define how H3K64me3 on the lateral surface of the histone octamer integrates within the heterochromatinization cascade. Our data suggest that enrichment of H3K64me3 at pericentromeric chromatin foci is dependent on H3K9me3 but independent of a number of central factors such as heterochromatin protein 1, DNA methyltransferases and Suv4-20h histone methyltransferases. Our results support a model in which pericentromeric heterochromatin foci are formed along distinct pathways upon H3K9 trimethylation, involving H3K64me3 to potentially stabilize DNA-histone interactions, as well as sequential recruitment of repressive histone tail and DNA modifications. We hence suggest that multiple mechanisms ensure heterochromatin integrity at pericentromeres, with H3K64me3 as an important factor.
为了确保基因组的稳定性，着丝粒区域通过特定的“表观遗传”因素和修饰组合，被压缩成一个密集的异染色质结构。级联途径负责建立涉及染色质修饰物和“读取器”的着丝粒染色质，例如 H3K9 组蛋白甲基转移酶（Suv）39h 和异染色质蛋白 1。在这里，我们定义了组蛋白八聚体侧面的 H3K64me3 如何整合到异染色质化级联中。我们的数据表明，着丝粒染色质焦点处 H3K64me3 的富集依赖于 H3K9me3，但不依赖于许多中央因素，如异染色质蛋白 1、DNA 甲基转移酶和 Suv4-20h 组蛋白甲基转移酶。我们的结果支持这样一种模型，即 H3K9 三甲基化后，沿着不同的途径形成着丝粒异染色质焦点，涉及 H3K64me3 以潜在地稳定 DNA-组蛋白相互作用，以及抑制性组蛋白尾部和 DNA 修饰的顺序募集。因此，我们认为多种机制可确保着丝粒处异染色质的完整性，其中 H3K64me3 是一个重要因素。
