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Centromere formation remodels chromatin fibre structure

By Catherine Naughton, Covadonga Huidobro, Claudia R Catacchio, Adam Buckle, Graeme R. Grimes, Ryu-Suke Nozawa, Stefania Purgato, Mariano Rocchi, Nick Gilbert

Posted 02 Aug 2021
bioRxiv DOI: 10.1101/2021.08.01.454615

Human centromeric chromatin is assembled from CENP-A nucleosomes and repetitive -satellite DNA sequences and provides a foundation for kinetochore assembly in mitosis. Biophysical experiments led to a hypothesis that the repetitive DNA sequences form a highly folded chromatin scaffold necessary for function, but this idea was revised when fully functional evolutionary new centromeres (ENCs) or neocentromeres were found to form on non-repetitive DNA. To understand if centromeres have a special chromatin structure we have genetically isolated a single human chromosome harbouring a neocentromere and investigated its organisation. The centromere core is enriched in RNA pol II, active epigenetic marks and remodelled by transcription to form a negatively supercoiled open chromatin domain. In contrast, centromerisation causes a spreading of repressive epigenetic marks to flanking regions, delimited by H3K27me3 polycomb boundaries and divergent genes. The flanking domain is partially remodelled to form compact chromatin, with characteristics similar to satellite-containing pericentromeric chromatin, but exhibits low level genomic instability. We provide a model for centromere chromatin structure and suggest that open chromatin provides a foundation for a stable kinetochore whilst pericentromeric heterochromatin generates surrounding mechanical rigidity.

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