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Induction of spontaneous human neocentromere formation and long-term maturation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE155829 | GEO | 2021/01/08

REPOSITORIES: GEO

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Induction of spontaneous human neocentromere formation and long-term maturation.

Project description:Human centromeres form primarily on ?-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.

| S-EPMC7812830 | biostudies-literature

Induction of spontaneous human neocentromere formation and long-term maturation (QuantChIP-Seq)

Project description:We report a chromosome engineering system for human neocentromere formation and characterize the first experimentally generated human neocentromere. Neocentromere formation promotes local H3K9me3 eviction and cohesin and RNA polymerase II recruitment. Long-term culture results in gradual maturation of the inner centromere.

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Induction of spontaneous human neocentromere formation and long-term maturation

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Induction of spontaneous human neocentromere formation and long-term maturation (QuantChIP-Seq)

Project description:Induction of spontaneous human neocentromere formation and long-term maturation (QuantChIP-Seq)

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