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Human centromere repositioning activates transcription and opens chromatin fibre structure

Catherine Naughton, Covadonga Huidobro, Claudia R. Catacchio, Adam Buckle, Graeme R. Grimes, Ryu-Suke Nozawa, Stefania Purgato, Mariano Rocchi and Nick Gilbert ()
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Catherine Naughton: The University of Edinburgh
Covadonga Huidobro: The University of Edinburgh
Claudia R. Catacchio: The University of Edinburgh
Adam Buckle: The University of Edinburgh
Graeme R. Grimes: The University of Edinburgh
Ryu-Suke Nozawa: The University of Edinburgh
Stefania Purgato: The University of Edinburgh
Mariano Rocchi: University of Bari
Nick Gilbert: The University of Edinburgh

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Human centromeres appear as constrictions on mitotic chromosomes and form a platform for kinetochore assembly in mitosis. Biophysical experiments led to a suggestion that repetitive DNA at centromeric regions form a compact scaffold necessary for function, but this was revised when neocentromeres were discovered on non-repetitive DNA. To test whether centromeres have a special chromatin structure we have analysed the architecture of a neocentromere. Centromere repositioning is accompanied by RNA polymerase II recruitment and active transcription to form a decompacted, negatively supercoiled domain enriched in ‘open’ chromatin fibres. In contrast, centromerisation causes a spreading of repressive epigenetic marks to surrounding regions, delimited by H3K27me3 polycomb boundaries and divergent genes. This flanking domain is transcriptionally silent and partially remodelled to form ‘compact’ chromatin, similar to satellite-containing DNA sequences, and exhibits genomic instability. We suggest transcription disrupts chromatin to provide a foundation for kinetochore formation whilst compact pericentromeric heterochromatin generates mechanical rigidity.

Date: 2022
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DOI: 10.1038/s41467-022-33426-2

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