期刊
EMBO JOURNAL
卷 39, 期 20, 页码 -出版社
WILEY
DOI: 10.15252/embj.2020105505
关键词
CENP-A; CENP-B; centromere; chromatin; chromosome segregation
资金
- Cell and Tissue Imaging facility (PICT-IBiSA, French National Research Infrastructure France-BioImaging) [ANR10-INBS-04]
- National Science Foundation Graduate Research Fellowship [DGE-1644868]
- National Institutes of Health [R01 GM124041]
- AIRC
- I. Curie and a Seneca post-doctoral fellowship [20941/PD/18]
- LABEX DCBIOL
- ANR [ANR-17-CE15-0025-01, ANR-18-CE92-0022-01, ANR-19-CE15-0018-01]
- INSERM [19CS007-00]
- ANRS
- Labex Cell(n)Scale
- Institut Curie
- ATIP-Avenir ITMO Cancer 2015 program
- program Investissements d'Avenir [ANR-10-LABX-0038, ANR-10-IDEX-0001-02 PSL]
- Emergence grant 2018 from the city of Paris
- European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie grant [666003]
- French foundation for medical research (FRM) [FDT201904008185]
- Agence Nationale de la Recherche (ANR) [ANR-19-CE15-0018, ANR-18-CE92-0022, ANR-17-CE15-0025, ANR-10-LABX-0038] Funding Source: Agence Nationale de la Recherche (ANR)
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 promotingde novoCENP-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.
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