151. A genetic memory initiates the epigenetic loop necessary to preserve centromere position
- Author
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Daniele Fachinetti, Sebastian Hoffmann, Florian Chardon, Helena M Izquierdo, Solène Hervé, Nicolas Manel, Marie Dumont, Veer Keizer, Shannon M. McNulty, Beth A. Sullivan, Riccardo Gamba, Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Immunité et cancer (U932), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Duke University Medical Center, Institut Curie [Paris], Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Fachinetti, Daniele
- Subjects
Neocentromere ,[SDV]Life Sciences [q-bio] ,Population ,chromosome segregation ,macromolecular substances ,Biology ,Chromatin, Epigenetics, Genomics & Functional Genomics ,General Biochemistry, Genetics and Molecular Biology ,Article ,Chromosome segregation ,03 medical and health sciences ,Histone H3 ,0302 clinical medicine ,Transcription & Genomics ,Centromere ,Epigenetics ,education ,Molecular Biology ,Genetic memory (biology) ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,General Immunology and Microbiology ,General Neuroscience ,Cell Cycle ,Articles ,Chromatin ,Cell biology ,[SDV] Life Sciences [q-bio] ,centromere ,chromatin ,CENP-A ,030217 neurology & neurosurgery ,CENP‐A ,CENP-B ,CENP‐B - 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‐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., Rapid removal and reactivation of CENP‐A defines the temporal cascade of events necessary to maintain centromere position, with DNA‐bound CENP‐B providing memory and preventing movement of centromere position.
- Published
- 2020