Histone hyperacetylation in mitosis prevents sister chromatid separation and produces chromosome segregation defects

Daniela Cimini, Marta Mattiuzzo, Liliana Torosantucci, Francesca Degrassi

Research output: Contribution to journalArticle

Abstract

Posttranslational modifications of core histones contribute to driving changes in chromatin conformation and compaction. Herein, we investigated the role of histone deacetylation on the mitotic process by inhibiting histone deacetylases shortly before mitosis in human primary fibroblasts. Cells entering mitosis with hyperacetylated histones displayed altered chromatin conformation associated with decreased reactivity to the anti-Ser 10 phospho H3 antibody, increased recruitment of protein phosphatase 1-δ on mitotic chromosomes, and depletion of heterochromatin protein 1 from the centromeric heterochromatin. Inhibition of histone deacetylation before mitosis produced defective chromosome condensation and impaired mitotic progression in living cells, suggesting that improper chromosome condensation may induce mitotic checkpoint activation. In situ hybridization analysis on anaphase cells demonstrated the presence of chromatin bridges, which were caused by persisting cohesion along sister chromatid arms after centromere separation. Thus, the presence of hyperacetylated chromatin during mitosis impairs proper chromosome condensation during the pre-anaphase stages, resulting in poor sister chromatid resolution. Lagging chromosomes consisting of single or paired sisters were also induced by the presence of hyperacetylated histones, indicating that the less constrained centromeric organization associated with heterochromatin protein 1 depletion may promote the attachment of kinetochores to microtubules coming from both poles.

Original languageEnglish
Pages (from-to)3821-3833
Number of pages13
JournalMolecular Biology of the Cell
Volume14
Issue number9
DOIs
Publication statusPublished - Sep 1 2003

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

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