CENP-A: A Histone H3 Variant with Key Roles in Centromere Architecture in Healthy and Diseased States

Overview

Journal Results Probl Cell Differ

Specialty Cell Biology

Date 2022 Nov 8

PMID 36348109

Authors

Daniel Jeffery

Marina Lochhead

Genevieve Almouzni

Affiliations

Soon will be listed here.

Abstract

Centromeres are key architectural components of chromosomes. Here, we examine their construction, maintenance, and functionality. Focusing on the mammalian centromere- specific histone H3 variant, CENP-A, we highlight its coevolution with both centromeric DNA and its chaperone, HJURP. We then consider CENP-A de novo deposition and the importance of centromeric DNA recently uncovered with the added value from new ultra-long-read sequencing. We next review how to ensure the maintenance of CENP-A at the centromere throughout the cell cycle. Finally, we discuss the impact of disrupting CENP-A regulation on cancer and cell fate.

Citing Articles

The cell-cycle choreography of H3 variants shapes the genome.

Delaney K, Weiss N, Almouzni G Mol Cell. 2023; 83(21):3773-3786.

PMID: 37734377 PMC: 10621666. DOI: 10.1016/j.molcel.2023.08.030.

References

Akera T, Trimm E, Lampson M . Molecular Strategies of Meiotic Cheating by Selfish Centromeres. Cell. 2019; 178(5):1132-1144.e10. PMC: 6731994. DOI: 10.1016/j.cell.2019.07.001. View

Alcobia I, Dilao R, Parreira L . Spatial associations of centromeres in the nuclei of hematopoietic cells: evidence for cell-type-specific organizational patterns. Blood. 2000; 95(5):1608-15. View

Alcobia I, Quina A, Neves H, Clode N, Parreira L . The spatial organization of centromeric heterochromatin during normal human lymphopoiesis: evidence for ontogenically determined spatial patterns. Exp Cell Res. 2003; 290(2):358-69. DOI: 10.1016/s0014-4827(03)00335-5. View

Aldrup-MacDonald M, Kuo M, Sullivan L, Chew K, Sullivan B . Genomic variation within alpha satellite DNA influences centromere location on human chromosomes with metastable epialleles. Genome Res. 2016; 26(10):1301-1311. PMC: 5052062. DOI: 10.1101/gr.206706.116. View

Altemose N, Logsdon G, Bzikadze A, Sidhwani P, Langley S, Caldas G . Complete genomic and epigenetic maps of human centromeres. Science. 2022; 376(6588):eabl4178. PMC: 9233505. DOI: 10.1126/science.abl4178. View

Ambartsumyan G, Gill R, Perez S, Conway D, Vincent J, Dalal Y . Centromere protein A dynamics in human pluripotent stem cell self-renewal, differentiation and DNA damage. Hum Mol Genet. 2010; 19(20):3970-82. PMC: 2947403. DOI: 10.1093/hmg/ddq312. View

Amor D, Bentley K, Ryan J, Perry J, Wong L, Slater H . Human centromere repositioning "in progress". Proc Natl Acad Sci U S A. 2004; 101(17):6542-7. PMC: 404081. DOI: 10.1073/pnas.0308637101. View

Bailey A, Panchenko T, Shabanowitz J, Lehman S, Bai D, Hunt D . Identification of the Post-translational Modifications Present in Centromeric Chromatin. Mol Cell Proteomics. 2015; 15(3):918-31. PMC: 4813710. DOI: 10.1074/mcp.M115.053710. View

Bakhoum S, Cantley L . The Multifaceted Role of Chromosomal Instability in Cancer and Its Microenvironment. Cell. 2018; 174(6):1347-1360. PMC: 6136429. DOI: 10.1016/j.cell.2018.08.027. View

10.

Barnhart M, Kuich P, Stellfox M, Ward J, Bassett E, Black B . HJURP is a CENP-A chromatin assembly factor sufficient to form a functional de novo kinetochore. J Cell Biol. 2011; 194(2):229-43. PMC: 3144403. DOI: 10.1083/jcb.201012017. View

11.

Barra V, Fachinetti D . The dark side of centromeres: types, causes and consequences of structural abnormalities implicating centromeric DNA. Nat Commun. 2018; 9(1):4340. PMC: 6194107. DOI: 10.1038/s41467-018-06545-y. View

12.

Barrera J, Kao L, Hammer R, Seemann J, Fuchs J, Megraw T . CDK5RAP2 regulates centriole engagement and cohesion in mice. Dev Cell. 2010; 18(6):913-26. PMC: 3078807. DOI: 10.1016/j.devcel.2010.05.017. View

13.

Bartholdi M . Nuclear distribution of centromeres during the cell cycle of human diploid fibroblasts. J Cell Sci. 1991; 99 ( Pt 2):255-63. DOI: 10.1242/jcs.99.2.255. View

14.

Bassett E, DeNizio J, Barnhart-Dailey M, Panchenko T, Sekulic N, Rogers D . HJURP uses distinct CENP-A surfaces to recognize and to stabilize CENP-A/histone H4 for centromere assembly. Dev Cell. 2012; 22(4):749-62. PMC: 3353549. DOI: 10.1016/j.devcel.2012.02.001. View

15.

Bergmann J, Rodriguez M, Martins N, Kimura H, Kelly D, Masumoto H . Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore. EMBO J. 2010; 30(2):328-40. PMC: 3025471. DOI: 10.1038/emboj.2010.329. View

16.

Bergmann J, Jakubsche J, Martins N, Kagansky A, Nakano M, Kimura H . Epigenetic engineering: histone H3K9 acetylation is compatible with kinetochore structure and function. J Cell Sci. 2012; 125(Pt 2):411-21. PMC: 3283876. DOI: 10.1242/jcs.090639. View

17.

Blank T, Becker P . The effect of nucleosome phasing sequences and DNA topology on nucleosome spacing. J Mol Biol. 1996; 260(1):1-8. DOI: 10.1006/jmbi.1996.0377. View

18.

Blower M, Sullivan B, Karpen G . Conserved organization of centromeric chromatin in flies and humans. Dev Cell. 2002; 2(3):319-30. PMC: 3192492. DOI: 10.1016/s1534-5807(02)00135-1. View

19.

Bobkov G, Gilbert N, Heun P . Centromere transcription allows CENP-A to transit from chromatin association to stable incorporation. J Cell Biol. 2018; 217(6):1957-1972. PMC: 5987708. DOI: 10.1083/jcb.201611087. View

20.

Boyarchuk E, Filipescu D, Vassias I, Cantaloube S, Almouzni G . The histone variant composition of centromeres is controlled by the pericentric heterochromatin state during the cell cycle. J Cell Sci. 2014; 127(Pt 15):3347-59. DOI: 10.1242/jcs.148189. View