Epigenetic Regulation of Centromere Function

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2020 Feb 3

PMID 32008088

Citations 11

Authors

Charmaine Yan Yu Wong

Bernard Chi Hang Lee

Karen Wing Yee Yuen

Affiliations

Soon will be listed here.

Abstract

The centromere is a specialized region on the chromosome that directs equal chromosome segregation. Centromeres are usually not defined by DNA sequences alone. How centromere formation and function are determined by epigenetics is still not fully understood. Active centromeres are often marked by the presence of centromeric-specific histone H3 variant, centromere protein A (CENP-A). How CENP-A is assembled into the centromeric chromatin during the cell cycle and propagated to the next cell cycle or the next generation to maintain the centromere function has been intensively investigated. In this review, we summarize current understanding of how post-translational modifications of CENP-A and other centromere proteins, centromeric and pericentric histone modifications, non-coding transcription and transcripts contribute to centromere function, and discuss their intricate relationships and potential feedback mechanisms.

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References

Ling Y, Yuen K . Centromeric non-coding RNA as a hidden epigenetic factor of the point centromere. Curr Genet. 2019; 65(5):1165-1171. DOI: 10.1007/s00294-019-00988-6. View

Bailey A, Panchenko T, Sathyan K, Petkowski J, Pai P, Bai D . Posttranslational modification of CENP-A influences the conformation of centromeric chromatin. Proc Natl Acad Sci U S A. 2013; 110(29):11827-32. PMC: 3718089. DOI: 10.1073/pnas.1300325110. View

Logsdon G, Barrey E, Bassett E, DeNizio J, Guo L, Panchenko T . Both tails and the centromere targeting domain of CENP-A are required for centromere establishment. J Cell Biol. 2015; 208(5):521-31. PMC: 4347640. DOI: 10.1083/jcb.201412011. View

Hayashi T, Fujita Y, Iwasaki O, Adachi Y, Takahashi K, Yanagida M . Mis16 and Mis18 are required for CENP-A loading and histone deacetylation at centromeres. Cell. 2004; 118(6):715-29. DOI: 10.1016/j.cell.2004.09.002. View

SHELBY R, Monier K, Sullivan K . Chromatin assembly at kinetochores is uncoupled from DNA replication. J Cell Biol. 2000; 151(5):1113-8. PMC: 2174364. DOI: 10.1083/jcb.151.5.1113. View

Camahort R, Li B, Florens L, Swanson S, Washburn M, Gerton J . Scm3 is essential to recruit the histone h3 variant cse4 to centromeres and to maintain a functional kinetochore. Mol Cell. 2007; 26(6):853-65. DOI: 10.1016/j.molcel.2007.05.013. View

Muchardt C, Guilleme M, Seeler J, Trouche D, Dejean A, Yaniv M . Coordinated methyl and RNA binding is required for heterochromatin localization of mammalian HP1alpha. EMBO Rep. 2002; 3(10):975-81. PMC: 1307621. DOI: 10.1093/embo-reports/kvf194. View

Catania S, Pidoux A, Allshire R . Sequence features and transcriptional stalling within centromere DNA promote establishment of CENP-A chromatin. PLoS Genet. 2015; 11(3):e1004986. PMC: 4349457. DOI: 10.1371/journal.pgen.1004986. View

Silva M, Bodor D, Stellfox M, Martins N, Hochegger H, Foltz D . Cdk activity couples epigenetic centromere inheritance to cell cycle progression. Dev Cell. 2011; 22(1):52-63. DOI: 10.1016/j.devcel.2011.10.014. View

10.

Choy J, Acuna R, Au W, Basrai M . A role for histone H4K16 hypoacetylation in Saccharomyces cerevisiae kinetochore function. Genetics. 2011; 189(1):11-21. PMC: 3176121. DOI: 10.1534/genetics.111.130781. View

11.

Claycomb J, Batista P, Pang K, Gu W, Vasale J, van Wolfswinkel J . The Argonaute CSR-1 and its 22G-RNA cofactors are required for holocentric chromosome segregation. Cell. 2009; 139(1):123-34. PMC: 2766185. DOI: 10.1016/j.cell.2009.09.014. View

12.

Mravinac B, Sullivan L, Reeves J, Yan C, Kopf K, Farr C . Histone modifications within the human X centromere region. PLoS One. 2009; 4(8):e6602. PMC: 2719913. DOI: 10.1371/journal.pone.0006602. View

13.

Bade D, Pauleau A, Wendler A, Erhardt S . The E3 ligase CUL3/RDX controls centromere maintenance by ubiquitylating and stabilizing CENP-A in a CAL1-dependent manner. Dev Cell. 2014; 28(5):508-19. DOI: 10.1016/j.devcel.2014.01.031. View

14.

Spiller F, Medina-Pritchard B, Abad M, Wear M, Molina O, Earnshaw W . Molecular basis for Cdk1-regulated timing of Mis18 complex assembly and CENP-A deposition. EMBO Rep. 2017; 18(6):894-905. PMC: 5452045. DOI: 10.15252/embr.201643564. View

15.

Amor D, Choo K . Neocentromeres: role in human disease, evolution, and centromere study. Am J Hum Genet. 2002; 71(4):695-714. PMC: 378529. DOI: 10.1086/342730. View

16.

Gopalakrishnan S, Sullivan B, Trazzi S, Valle G, Robertson K . DNMT3B interacts with constitutive centromere protein CENP-C to modulate DNA methylation and the histone code at centromeric regions. Hum Mol Genet. 2009; 18(17):3178-93. PMC: 2722982. DOI: 10.1093/hmg/ddp256. View

17.

Thakur J, Sanyal K . Efficient neocentromere formation is suppressed by gene conversion to maintain centromere function at native physical chromosomal loci in Candida albicans. Genome Res. 2013; 23(4):638-52. PMC: 3613581. DOI: 10.1101/gr.141614.112. View

18.

Hall I, Shankaranarayana G, Noma K, Ayoub N, Cohen A, Grewal S . Establishment and maintenance of a heterochromatin domain. Science. 2002; 297(5590):2232-7. DOI: 10.1126/science.1076466. View

19.

Furuyama S, Biggins S . Centromere identity is specified by a single centromeric nucleosome in budding yeast. Proc Natl Acad Sci U S A. 2007; 104(37):14706-11. PMC: 1976213. DOI: 10.1073/pnas.0706985104. View

20.

Topp C, Zhong C, Dawe R . Centromere-encoded RNAs are integral components of the maize kinetochore. Proc Natl Acad Sci U S A. 2004; 101(45):15986-91. PMC: 528775. DOI: 10.1073/pnas.0407154101. View