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Induction of spontaneous human neocentromere formation and long-term maturation

Abstract : Human centromeres form primarily on α-satellite DNA but sporadically arise de novo at naive ectopic loci, creating neocentromeres. Centromere inheritance is driven primarily by chromatin containing the histone H3 variant CENP-A. Here, we report a chromosome engineering system for neocentromere formation in human cells and characterize the first experimentally induced human neocentromere at a naive locus. The spontaneously formed neocentromere spans a gene-poor 100-kb domain enriched in histone H3 lysine 9 trimethylated (H3K9me3). Long-read sequencing revealed this neocentromere was formed by purely epigenetic means and assembly of a functional kinetochore correlated with CENP-A seeding, eviction of H3K9me3 and local accumulation of mitotic cohesin and RNA polymerase II. At formation, the young neocentromere showed markedly reduced chromosomal passenger complex (CPC) occupancy and poor sister chromatin cohesion. However, long-term tracking revealed increased CPC assembly and low-level transcription providing evidence for centromere maturation over time.
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https://hal-cnrs.archives-ouvertes.fr/hal-03452716
Contributor : Daniele Fachinetti Connect in order to contact the contributor
Submitted on : Monday, November 29, 2021 - 3:25:31 PM
Last modification on : Thursday, December 16, 2021 - 1:10:23 PM

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Marina Murillo-Pineda, Luis Valente, Marie Dumont, João Mata, Daniele Fachinetti, et al.. Induction of spontaneous human neocentromere formation and long-term maturation. Journal of Cell Biology, Rockefeller University Press, 2021, 220 (3), ⟨10.1083/jcb.202007210⟩. ⟨hal-03452716⟩

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