Journal
NUCLEIC ACIDS RESEARCH
Volume 47, Issue 3, Pages 1051-1069Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gky1298
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Funding
- Televie-FNRS [7.4633.16]
- Agence Nationale pour la Recherche [ANR-10-LABX-0030, ANR-12-BSV5-0017, ANR-14-CE09-0019, ANR-16-CE12-0013, ANR-17-CE11-0019, ANR-18-CE12-00XX]
- La Ligue Nationale contre le Cancer (Equipe labellisee)
- Fondation pour la Recherche Medicale (FRM, 'Epigenetique et Stabilite du Genome' Program)
- Institut National du Cancer
- Association pour la Recherche sur le Cancer
- INSERM
- CNRS
- Universite Grenoble Alpes
- Luxembourg Institute of Health
- Strasbourg University
- Agence Nationale de la Recherche (ANR) [ANR-16-CE12-0013, ANR-14-CE09-0019, ANR-10-LABX-0030, ANR-17-CE11-0019, ANR-12-BSV5-0017] Funding Source: Agence Nationale de la Recherche (ANR)
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The histone H3 variant CENP-A confers epigenetic identity to the centromere and plays crucial roles in the assembly and function of the kinetochore, thus ensuring proper segregation of our chromosomes. CENP-A containing nucleosomes exhibit unique structural specificities and lack the complex profile of gene expression-associated histone posttranslational modifications found in canonical histone H3 and the H3.3 variant. CENP-A mislocalization into noncentromeric regions resulting from its overexpression leads to chromosomal segregation aberrations and genome instability. Overexpression of CENP-A is a feature of many cancers and is associated with malignant progression and poor outcome. The recent years have seen impressive progress in our understanding of the mechanisms that orchestrate CENP-A deposition at native centromeres and ectopic loci. They have witnessed the description of novel, heterotypic CENP-A/H3.3 nucleosome particles and the exploration of the phenotypes associated with the deregulation of CENP-A and its chaperones in tumor cells. Here, we review the structural specificities of CENP-A nucleosomes, the epigenetic features that characterize the centrochromatin and the mechanisms and factors that orchestrate CENP-A deposition at centromeres. We then review our knowledge of CENP-A ectopic distribution, highlighting experimental strategies that have enabled key discoveries. Finally, we discuss the implications of deregulated CENP-A in cancer.
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