期刊
GENES & DEVELOPMENT
卷 30, 期 11, 页码 1313-1326出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.275073.115
关键词
centromere; CENP; histone chaperone; mitosis
资金
- European Commission FP7 Marie Curie Intra European Fellowship CenHFD
- La Ligue Nationale Contre le Cancer (Equipe labellisee Ligue)
- European Commission Network of Excellence EpiGeneSys [HEALTH-F4-2010-257082]
- ERC Advanced Grant Eccentric [2009-AdG_20090506]
- European Commission Large-Scale Integrating Project (MODHEP) [FP7_HEALTH-2010-259743, ANR-11-LABX-0044_DEEP, ANR-10-IDEX-0001-02 PSL]
- ANR CHAPINHIB [ANR-11-LABX-0044_DEEP, ANR-12-BSV5-0022-02]
- ANR Epicure [ANR-14-CE16-0009]
- ANR CELLECTCHIP [ANR-14-CE10-0013]
- Aviesan-ITMO cancer project Epigenomics of breast cancer
- STARR Foundation
- Leukemia and Lymphoma Foundation
- Memorial Sloan-Kettering Cancer Center Support Grant/Core Grant [P30 CA008748]
- Science Foundation Ireland [05/RP1/B793, 12/IA/1370]
- Region Ile-de-France [2013-2-EML-02-ICR-1, 2014-2-INV-04-ICR-1]
- Fondation pour la Recherche Medicale [DGE 20121125630]
- Agence Nationale de la Recherche (ANR) [ANR-14-CE10-0013] Funding Source: Agence Nationale de la Recherche (ANR)
- Science Foundation Ireland (SFI) [12/IA/1370, 05/RP1/B793] Funding Source: Science Foundation Ireland (SFI)
The CENP-T/-W histone fold complex, as an integral part of the inner kinetochore, is essential for building a proper kinetochore at the centromere in order to direct chromosome segregation during mitosis. Notably, CENP-T/-W is not inherited at centromeres, and new deposition is absolutely required at each cell cycle for kinetochore function. However, the mechanisms underlying this new deposition of CENP-T/-W at centromeres are unclear. Here, we found that CENP-T deposition at centromeres is uncoupled from DNA synthesis. We identified Spt16 and SSRP1, subunits of the H2A-H2B histone chaperone facilitates chromatin transcription (FACT), as CENP-W binding partners through a proteomic screen. We found that the C-terminal region of Spt16 binds specifically to the histone fold region of CENP-T/-W. Furthermore, depletion of Spt16 impairs CENP-T and CENP-W deposition at endogenous centromeres, and site-directed targeting of Spt16 alone is sufficient to ensure local de novo CENP-T accumulation. We propose a model in which the FACT chaperone stabilizes the soluble CENP-T/-W complex in the cell and promotes dynamics of exchange, enabling CENP-T/-W deposition at centromeres.
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