Year: 2016
Type: preprint
Abstract: 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.
Source: Genes & Development
Authors: Lisa Prendergast, Sebastian Müller, Yiwei Liu, Hongda Huang, Florent Dingli, Damarys Loew, Isabelle Vassias, Dinshaw J. Patel, Kevin F. Sullivan, Geneviève Almouzni
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: Leukemia and Lymphoma Society, Memorial Sloan-Kettering Cancer Center, Starr Foundation, Danish Cancer Society Research Center, European Commission, Science Foundation Ireland, Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Ligue Contre le Cancer, European Research Council, National Cancer Institute
Awards: G145140745, G2051006376, G2240933695, Paris Sciences et Lettres, Development of SUV39H1/H2 inhibitors for immune modulation and cancer therapy, G2892421564, G289723095, G3489752117, G365594388, G3657628968, Epigenetics towards systems biology, G3953683450, G4190806336, G4231756678, Systems biology of liver cancer: an integrative genomic-epigenomic approach, G4263741544, G453822889, G471331628, Assembly of centromeric chromatin and gene silencing comparments, Structure and assembly of vertebrate kinetochore-associated chromatin, INDIVIDUAL CELL SELECTION TO MONITOR THE DYNAMICS OF EPIGENETIC MARKS DURING S-PHASE AND EARLY MAMMALIAN EMBRYOGENESIS., G6048653459, G6702880738, G6759105742, G6764730869, Inhibiting Chromatin Assembly by Targeting Histone Chaperones, G7144604388, G7240651115, G782245399, Développement, Epigénèse, Epigénétique et potentiel de vie, Cancer Center Support Grant
OpenAlex ID: W6959812341