Format

Send to

Choose Destination
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.

Author information

1
NORLUX Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health (LIH), 84 Val Fleuri, L-1526 Luxembourg, Luxembourg.
2
Université Grenoble Alpes, CNRS UMR 5309, INSERM U1209, Institute for Advanced Biosciences (IAB), Site Santé-Allée des Alpes, 38700 La Tronche, France.
3
Izmir Biomedicine and Genome Center, İzmir, Turkey.
4
Département de Génomique Fonctionnelle et Cancer, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, CNRS, INSERM, 67404 Illkirch Cedex, France.

Abstract

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.

PMID:
30590707
PMCID:
PMC6379705
DOI:
10.1093/nar/gky1298
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center