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

dc.contributor.author

Hoffmann, Sebastian

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Izquierdo, Helena M

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Gamba, Riccardo

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Chardon, Florian

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Dumont, Marie

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Keizer, Veer

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Hervé, Solène

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McNulty, Shannon M

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Sullivan, Beth A

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Manel, Nicolas

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Fachinetti, Daniele

dc.date.accessioned

2022-04-01T14:29:30Z

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2022-04-01T14:29:30Z

dc.date.issued

2020-10

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2022-04-01T14:29:29Z

dc.description.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.

dc.identifier.issn

0261-4189

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1460-2075

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https://hdl.handle.net/10161/24765

dc.language

eng

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EMBO

dc.relation.ispartof

The EMBO journal

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10.15252/embj.2020105505

dc.subject

CD4-Positive T-Lymphocytes

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Cell Line, Tumor

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Centromere

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Nucleosomes

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Humans

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Chromosomal Proteins, Non-Histone

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RNA, Small Interfering

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In Situ Hybridization, Fluorescence

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Gene Targeting

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Computational Biology

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Cell Cycle

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Chromosome Segregation

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Epigenesis, Genetic

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Centromere Protein B

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CRISPR-Cas Systems

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Centromere Protein A

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Sullivan, Beth A|0000-0001-5216-4603

pubs.begin-page

e105505

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20

pubs.organisational-group

Duke

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School of Medicine

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Basic Science Departments

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Institutes and Centers

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Molecular Genetics and Microbiology

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Duke Cancer Institute

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Institutes and Provost's Academic Units

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Initiatives

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Duke Science & Society

pubs.publication-status

Published

pubs.volume

39

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