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Nucleic Acids Res. 2019 Feb 20;47(3):1051-1069. doi: 10.1093/nar/gky1298.

Centromeric and ectopic assembly of CENP-A chromatin in health and cancer: old marks and new tracks.

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NORLUX Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health (LIH), 84 Val Fleuri, L-1526 Luxembourg, Luxembourg.
Université Grenoble Alpes, CNRS UMR 5309, INSERM U1209, Institute for Advanced Biosciences (IAB), Site Santé-Allée des Alpes, 38700 La Tronche, France.
Izmir Biomedicine and Genome Center, İzmir, Turkey.
Département de Génomique Fonctionnelle et Cancer, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, CNRS, INSERM, 67404 Illkirch Cedex, France.


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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