A Genetic Memory Initiates the Epigenetic Loop Necessary to Preserve Centromere Position

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2020 Sep 18

PMID 32945564

Citations 15

Authors

Sebastian Hoffmann

Helena M Izquierdo

Riccardo Gamba

Florian Chardon

Marie Dumont

Veer Keizer

Solene Herve

Shannon M McNulty

Beth A Sullivan

Nicolas Manel

Daniele Fachinetti

Affiliations

Soon will be listed here.

Abstract

Centromeres are built on repetitive DNA sequences (CenDNA) and a specific chromatin enriched with the histone H3 variant CENP-A, the epigenetic mark that identifies centromere position. Here, we interrogate the importance of CenDNA in centromere specification by developing a system to rapidly remove and reactivate CENP-A (CENP-A ). Using this system, we define the temporal cascade of events necessary to maintain centromere position. We unveil that CENP-B bound to CenDNA provides memory for maintenance on human centromeres by promoting de novo CENP-A deposition. Indeed, lack of CENP-B favors neocentromere formation under selective pressure. Occasionally, CENP-B triggers centromere re-activation initiated by CENP-C, but not CENP-A, recruitment at both ectopic and native centromeres. This is then sufficient to initiate the CENP-A-based epigenetic loop. Finally, we identify a population of CENP-A-negative, CENP-B/C-positive resting CD4 T cells capable to re-express and reassembles CENP-A upon cell cycle entry, demonstrating the physiological importance of the genetic memory.

Citing Articles

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References

Palmer D, ODay K, Wener M, Andrews B, Margolis R . A 17-kD centromere protein (CENP-A) copurifies with nucleosome core particles and with histones. J Cell Biol. 1987; 104(4):805-15. PMC: 2114441. DOI: 10.1083/jcb.104.4.805. View

Falk S, Lee J, Sekulic N, Sennett M, Lee T, Black B . CENP-C directs a structural transition of CENP-A nucleosomes mainly through sliding of DNA gyres. Nat Struct Mol Biol. 2016; 23(3):204-208. PMC: 4893769. DOI: 10.1038/nsmb.3175. View

Hori T, Shang W, Takeuchi K, Fukagawa T . The CCAN recruits CENP-A to the centromere and forms the structural core for kinetochore assembly. J Cell Biol. 2013; 200(1):45-60. PMC: 3542802. DOI: 10.1083/jcb.201210106. View

Fachinetti D, Han J, McMahon M, Ly P, Abdullah A, Wong A . DNA Sequence-Specific Binding of CENP-B Enhances the Fidelity of Human Centromere Function. Dev Cell. 2015; 33(3):314-27. PMC: 4421092. DOI: 10.1016/j.devcel.2015.03.020. View

Li H, Durbin R . Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009; 25(14):1754-60. PMC: 2705234. DOI: 10.1093/bioinformatics/btp324. View

Okada T, Ohzeki J, Nakano M, Yoda K, Brinkley W, Larionov V . CENP-B controls centromere formation depending on the chromatin context. Cell. 2007; 131(7):1287-300. DOI: 10.1016/j.cell.2007.10.045. 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

Ohzeki J, Shono N, Otake K, Martins N, Kugou K, Kimura H . KAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing Suv39h1-Mediated Centromere Inactivation. Dev Cell. 2016; 37(5):413-27. PMC: 4906249. DOI: 10.1016/j.devcel.2016.05.006. View

Tokunaga M, Imamoto N, Sakata-Sogawa K . Highly inclined thin illumination enables clear single-molecule imaging in cells. Nat Methods. 2008; 5(2):159-61. DOI: 10.1038/nmeth1171. View

10.

Skene P, Henikoff S . An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites. Elife. 2017; 6. PMC: 5310842. DOI: 10.7554/eLife.21856. View

11.

Miga K . The Promises and Challenges of Genomic Studies of Human Centromeres. Prog Mol Subcell Biol. 2017; 56:285-304. DOI: 10.1007/978-3-319-58592-5_12. View

12.

Suzuki N, Nakano M, Nozaki N, Egashira S, Okazaki T, Masumoto H . CENP-B interacts with CENP-C domains containing Mif2 regions responsible for centromere localization. J Biol Chem. 2003; 279(7):5934-46. DOI: 10.1074/jbc.M306477200. View

13.

Ramirez F, Ryan D, Gruning B, Bhardwaj V, Kilpert F, Richter A . deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 2016; 44(W1):W160-5. PMC: 4987876. DOI: 10.1093/nar/gkw257. View

14.

Ross J, Woodlief K, Sullivan B . Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres. Epigenetics Chromatin. 2016; 9:20. PMC: 4888493. DOI: 10.1186/s13072-016-0071-7. View

15.

Hori T, Amano M, Suzuki A, Backer C, Welburn J, Dong Y . CCAN makes multiple contacts with centromeric DNA to provide distinct pathways to the outer kinetochore. Cell. 2008; 135(6):1039-52. DOI: 10.1016/j.cell.2008.10.019. View

16.

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

17.

Otake K, Ohzeki J, Shono N, Kugou K, Okazaki K, Nagase T . CENP-B creates alternative epigenetic chromatin states permissive for CENP-A or heterochromatin assembly. J Cell Sci. 2020; 133(15). PMC: 7438015. DOI: 10.1242/jcs.243303. View

18.

Saldivar J, Hamperl S, Bocek M, Chung M, Bass T, Cisneros-Soberanis F . An intrinsic S/G checkpoint enforced by ATR. Science. 2018; 361(6404):806-810. PMC: 6365305. DOI: 10.1126/science.aap9346. View

19.

Guse A, Carroll C, Moree B, Fuller C, Straight A . In vitro centromere and kinetochore assembly on defined chromatin templates. Nature. 2011; 477(7364):354-8. PMC: 3175311. DOI: 10.1038/nature10379. View

20.

Xiao H, Wang F, Wisniewski J, Shaytan A, Ghirlando R, FitzGerald P . Molecular basis of CENP-C association with the CENP-A nucleosome at yeast centromeres. Genes Dev. 2017; 31(19):1958-1972. PMC: 5710141. DOI: 10.1101/gad.304782.117. View