Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
Nat Cell Biol. 2011 Jun 19;13(7):799-808. doi: 10.1038/ncb2272.
The centromere-specific histone H3 variant CENH3 (also known as CENP-A) is considered to be an epigenetic mark for establishment and propagation of centromere identity. Pulse induction of CENH3 (Drosophila CID) in Schneider S2 cells leads to its incorporation into non-centromeric regions and generates CID islands that resist clearing from chromosome arms for multiple cell generations. We demonstrate that CID islands represent functional ectopic kinetochores, which are non-randomly distributed on the chromosome and show a preferential localization near telomeres and pericentric heterochromatin in transcriptionally silent, intergenic chromatin domains. Although overexpression of heterochromatin protein 1 (HP1) or increasing histone acetylation interferes with CID island formation on a global scale, induction of a locally defined region of synthetic heterochromatin by targeting HP1-LacI fusions to stably integrated Lac operator arrays produces a proximal hotspot for CID deposition. These data indicate that the characteristics of regions bordering heterochromatin promote de novo kinetochore assembly and thereby contribute to centromere identity.
着丝粒特异性组蛋白 H3 变体 CENH3（也称为 CENP-A）被认为是建立和传播着丝粒身份的表观遗传标记。在 Schneider S2 细胞中诱导 CENH3（果蝇 CID）脉冲会导致其掺入非着丝粒区域，并产生 CID 岛，这些 CID 岛可抵抗多个细胞世代从染色体臂上清除。我们证明 CID 岛代表功能性异位着丝粒，这些着丝粒在染色体上呈非随机分布，并在转录沉默的基因间染色质区域中优先定位于端粒和着丝粒异染色质附近。尽管异染色质蛋白 1（HP1）的过表达或增加组蛋白乙酰化会干扰 CID 岛的全局形成，但通过将 HP1-LacI 融合靶向稳定整合的 Lac 操纵子阵列来诱导局部定义的合成异染色质区域会产生 CID 沉积的近端热点。这些数据表明，与异染色质相邻的区域的特征促进了新的着丝粒组装，从而有助于着丝粒身份。
