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A genetic memory initiates the epigenetic loop necessary to preserve centromere position

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 OFF/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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https://hal-cnrs.archives-ouvertes.fr/hal-03452706
Contributor : Daniele Fachinetti Connect in order to contact the contributor
Submitted on : Saturday, November 27, 2021 - 12:30:27 PM
Last modification on : Sunday, June 26, 2022 - 3:21:49 AM
Long-term archiving on: : Monday, February 28, 2022 - 6:18:24 PM

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Sebastian Hoffmann, Helena M Izquierdo, Riccardo Gamba, Florian Chardon, Marie Dumont, et al.. A genetic memory initiates the epigenetic loop necessary to preserve centromere position. EMBO Journal, EMBO Press, 2020, 39, ⟨10.15252/embj.2020105505⟩. ⟨hal-03452706⟩

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