Brero Alessandro, Easwaran Hariharan P, Nowak Danny, Grunewald Ingrid, Cremer Thomas, Leonhardt Heinrich, Cardoso M Cristina
Department of Biology II, Ludwig Maximilians University Munich, 82152 Planegg-Martinsried, Germany.
J Cell Biol. 2005 Jun 6;169(5):733-43. doi: 10.1083/jcb.200502062.
Pericentric heterochromatin plays an important role in epigenetic gene regulation. We show that pericentric heterochromatin aggregates during myogenic differentiation. This clustering leads to the formation of large chromocenters and correlates with increased levels of the methyl CpG-binding protein MeCP2 and pericentric DNA methylation. Ectopic expression of fluorescently tagged MeCP2 mimicked this effect, causing a dose-dependent clustering of chromocenters in the absence of differentiation. MeCP2-induced rearrangement of heterochromatin occurred throughout interphase, did not depend on the H3K9 histone methylation pathway, and required the methyl CpG-binding domain (MBD) only. Similar to MeCP2, another methyl CpG-binding protein, MBD2, also increased during myogenic differentiation and could induce clustering of pericentric regions, arguing for functional redundancy. This MeCP2- and MBD2-mediated chromatin reorganization may thus represent a molecular link between nuclear genome topology and the epigenetic maintenance of cellular differentiation.
着丝粒周围异染色质在表观遗传基因调控中发挥着重要作用。我们发现，着丝粒周围异染色质在肌源性分化过程中会聚集。这种聚集导致形成大的染色中心，并且与甲基化CpG结合蛋白MeCP2水平的升高以及着丝粒周围DNA甲基化相关。荧光标记的MeCP2的异位表达模拟了这种效应，在未分化的情况下导致染色中心呈剂量依赖性聚集。MeCP2诱导的异染色质重排在整个间期发生，不依赖于H3K9组蛋白甲基化途径，并且仅需要甲基化CpG结合结构域（MBD）。与MeCP2类似，另一种甲基化CpG结合蛋白MBD2在肌源性分化过程中也增加，并且可以诱导着丝粒周围区域的聚集，这表明存在功能冗余。因此，这种由MeCP2和MBD2介导的染色质重组可能代表了核基因组拓扑结构与细胞分化表观遗传维持之间的分子联系。
