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Centromeres form a protein scaffold defined by chromatin featuring CENP-A, a conserved histone H3 variant, in a manner largely independent of local DNA cis elements. CENP-A nucleosomes fulfill two essential criteria to epigenetically identify the centromere. They undergo self-templated duplication to reestablish centromeric chromatin following DNA replication. More importantly, CENP-A incorporated into centromeric chromatin is stably transmitted through consecutive cell division cycles. CENP-A nucleosomes have unique structural properties and binding partners that potentially explain their long lifetime in vivo. However, rather than a static building block, centromeric chromatin is dynamically regulated throughout the cell cycle, indicating that CENP-A stability is also controlled by external factors. We discuss recent insights and identify the outstanding questions on how dynamic control of the long-term stability of CENP-A ensures epigenetic centromere inheritance.<\/jats:p>","DOI":"10.1083\/jcb.202005099","type":"journal-article","created":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T13:34:10Z","timestamp":1600176850000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Stable inheritance of CENP-A chromatin: Inner strength versus dynamic control"],"prefix":"10.1083","volume":"219","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7326-7601","authenticated-orcid":false,"given":"Sreyoshi","family":"Mitra","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Oxford, Oxford, UK 1"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0561-213X","authenticated-orcid":true,"given":"Bharath","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Mechanistic Biology and Profiling, Discovery Sciences, R&D, AstraZeneca, Cambridge, UK 2"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2158-0345","authenticated-orcid":true,"given":"Lars E.T.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Oxford, Oxford, UK 1"}]}],"member":"291","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"2023072811464527000_bib1","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1101\/gad.256354.114","article-title":"Two distinct modes for propagation of histone PTMs across the cell cycle","volume":"29","author":"Alabert","year":"2015","journal-title":"Genes Dev"},{"key":"2023072811464527000_bib2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201948913","article-title":"CENP-C unwraps the human CENP-A nucleosome through the H2A C-terminal tail","volume":"20","author":"Ali-Ahmad","year":"2019","journal-title":"EMBO Rep"},{"key":"2023072811464527000_bib3","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1016\/j.cub.2019.06.062","article-title":"Structure of the Human Core Centromeric Nucleosome Complex","volume":"29","author":"Allu","year":"2019","journal-title":"Curr. 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