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

doi:https://doi.org/10.1038/s41467-022-33426-2

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 journal › Article › peer-review

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 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 language	English
Journal	Nature Communications
DOIs	https://doi.org/10.1038/s41467-022-33426-2
Publication status	Published - 24 Sep 2022

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title = "Human centromere repositioning activates transcription and opens chromatin fibre structure",

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 pol II recruitment and active transcription to form a decompacted, negatively supercoiled domain enriched in {\textquoteleft}open{\textquoteright} 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 {\textquoteleft}compact{\textquoteright} 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.",

author = "Catherine Naughton and Covadonga Huidobro and Catacchio, {Claudia Rita} and Adam Buckle and Grimes, {Graeme R} and Ryu-Suke Nozawa and Stefania Purgato and Mariano Rocchi and Nick Gilbert",

note = "Funding Information: We would like to thank all members of our groups for useful discussions and to Alison Pidoux and Jim Allan for critical comments on the manuscript. This work was funded by the UK Medical Research Council (MR/J00913X/1; MC_UU_00007/13) (NG). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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AU - Naughton, Catherine

AU - Huidobro, Covadonga

AU - Catacchio, Claudia Rita

AU - Buckle, Adam

AU - Grimes, Graeme R

AU - Nozawa, Ryu-Suke

AU - Purgato, Stefania

AU - Rocchi, Mariano

AU - Gilbert, Nick

N1 - Funding Information: We would like to thank all members of our groups for useful discussions and to Alison Pidoux and Jim Allan for critical comments on the manuscript. This work was funded by the UK Medical Research Council (MR/J00913X/1; MC_UU_00007/13) (NG). Publisher Copyright: © 2022, The Author(s).

PY - 2022/9/24

Y1 - 2022/9/24

N2 - 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.

AB - 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.

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DO - https://doi.org/10.1038/s41467-022-33426-2

M3 - Article

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

ER -

Human centromere repositioning activates transcription and opens chromatin fibre structure

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