Human centromere repositioning activates transcription and opens chromatin fibre structure

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 pol 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.
Original languageEnglish
JournalNature Communications
Publication statusPublished - 24 Sep 2022


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