A genetic memory initiates the epigenetic loop necessary to preserve centromere position.
Journal Article (Journal Article)
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-AOFF/ON ). 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.
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Duke Authors
Cited Authors
- Hoffmann, S; Izquierdo, HM; Gamba, R; Chardon, F; Dumont, M; Keizer, V; Hervé, S; McNulty, SM; Sullivan, BA; Manel, N; Fachinetti, D
Published Date
- October 15, 2020
Published In
Volume / Issue
- 39 / 20
Start / End Page
- e105505 -
PubMed ID
- 32945564
Pubmed Central ID
- PMC7560200
Electronic International Standard Serial Number (EISSN)
- 1460-2075
Digital Object Identifier (DOI)
- 10.15252/embj.2020105505
Language
- eng
Conference Location
- England