A genetic memory initiates the epigenetic loop necessary to preserve centromere position.
dc.contributor.author | Hoffmann, Sebastian | |
dc.contributor.author | Izquierdo, Helena M | |
dc.contributor.author | Gamba, Riccardo | |
dc.contributor.author | Chardon, Florian | |
dc.contributor.author | Dumont, Marie | |
dc.contributor.author | Keizer, Veer | |
dc.contributor.author | Hervé, Solène | |
dc.contributor.author | McNulty, Shannon M | |
dc.contributor.author | Sullivan, Beth A | |
dc.contributor.author | Manel, Nicolas | |
dc.contributor.author | Fachinetti, Daniele | |
dc.date.accessioned | 2022-04-01T14:29:30Z | |
dc.date.available | 2022-04-01T14:29:30Z | |
dc.date.issued | 2020-10 | |
dc.date.updated | 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 | |
dc.identifier.issn | 1460-2075 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | EMBO | |
dc.relation.ispartof | The EMBO journal | |
dc.relation.isversionof | 10.15252/embj.2020105505 | |
dc.subject | CD4-Positive T-Lymphocytes | |
dc.subject | Cell Line, Tumor | |
dc.subject | Centromere | |
dc.subject | Nucleosomes | |
dc.subject | Humans | |
dc.subject | Chromosomal Proteins, Non-Histone | |
dc.subject | RNA, Small Interfering | |
dc.subject | In Situ Hybridization, Fluorescence | |
dc.subject | Gene Targeting | |
dc.subject | Computational Biology | |
dc.subject | Cell Cycle | |
dc.subject | Chromosome Segregation | |
dc.subject | Epigenesis, Genetic | |
dc.subject | Centromere Protein B | |
dc.subject | CRISPR-Cas Systems | |
dc.subject | 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 | |
pubs.issue | 20 | |
pubs.organisational-group | Duke | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Basic Science Departments | |
pubs.organisational-group | Institutes and Centers | |
pubs.organisational-group | Molecular Genetics and Microbiology | |
pubs.organisational-group | Duke Cancer Institute | |
pubs.organisational-group | Institutes and Provost's Academic Units | |
pubs.organisational-group | Initiatives | |
pubs.organisational-group | Duke Science & Society | |
pubs.publication-status | Published | |
pubs.volume | 39 |
Files
Original bundle
- Name:
- The EMBO Journal - 2020 - Hoffmann - A genetic memory initiates the epigenetic loop necessary to preserve centromere.pdf
- Size:
- 3.83 MB
- Format:
- Adobe Portable Document Format
- Description:
- Published version