Hoffmann, SebastianIzquierdo, Helena MGamba, RiccardoChardon, FlorianDumont, MarieKeizer, VeerHervé, SolèneMcNulty, Shannon MSullivan, Beth AManel, NicolasFachinetti, Daniele2022-04-012022-04-012020-100261-41891460-2075https://hdl.handle.net/10161/24765Centromeres 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.CD4-Positive T-LymphocytesCell Line, TumorCentromereNucleosomesHumansChromosomal Proteins, Non-HistoneRNA, Small InterferingIn Situ Hybridization, FluorescenceGene TargetingComputational BiologyCell CycleChromosome SegregationEpigenesis, GeneticCentromere Protein BCRISPR-Cas SystemsCentromere Protein AJournal article2022-04-01