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A genetic memory initiates the epigenetic loop necessary to preserve centromere position
Author(s) -
Hoffmann Sebastian,
Izquierdo Helena M,
Gamba Riccardo,
Chardon Florian,
Dumont Marie,
Keizer Veer,
Hervé Solène,
McNulty Shan M,
Sullivan Beth A,
Manel Nicolas,
Fachinetti Daniele
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020105505
Subject(s) - marie curie , curie , library science , humanities , art history , physics , art , computer science , curie temperature , condensed matter physics , european union , ferromagnetism , business , economic policy
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.