Heterochromatin boundaries are hotspots for de novo kinetochore formation

Abstract

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. In most eukaryotes, the centromere is defined by epigenetic marks such as the histone H3 variant CENH3/CENP-A/CID. Ectopic induction of kinetochores in Drosophila S2 cells by CID overexpression leads to kinetochore assembly specifically in silent intergenic regions bordering heterochomratin, demonstrating a role for these domains in centromere identity.

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Olszak, A., van Essen, D., Pereira, A. et al. Heterochromatin boundaries are hotspots for de novo kinetochore formation. Nat Cell Biol 13, 799–808 (2011). https://doi.org/10.1038/ncb2272

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