Fachinetti, DanieleDiego Folco, H.Nechemia-Arbely, YaelValente, Luis P.Nguyen, KristenWong, Alex J.Zhu, QuanHolland, Andrew J.Desai, ArshadJansen, Lars E. T.Cleveland, Don W.2016-06-072016-06-072013-07-21Fachinetti, D., Diego Folco, H., Nechemia-Arbely, Y., Valente, L. P., Nguyen, K., Wong, A. J., Zhu, Q., Holland, A. J., Desai, A., Jansen, L. E. T., Cleveland, D. W. (2013). A two-step mechanism for epigenetic specification of centromere identity and function. Nat Cell Biol, 15(9), 1056–1066.http://hdl.handle.net/10400.7/625The basic determinant of chromosome inheritance, the centromere, is specified in many eukaryotes by an epigenetic mark. Using gene targeting in human cells and fission yeast, chromatin containing the centromere-specific histone H3 variant CENP-A is demonstrated to be the epigenetic mark that acts through a two-step mechanism to identify, maintain and propagate centromere function indefinitely. Initially, centromere position is replicated and maintained by chromatin assembled with the centromere-targeting domain (CATD) of CENP-A substituted into H3. Subsequently, nucleation of kinetochore assembly onto CATD-containing chromatin is shown to require either the amino- or carboxy-terminal tail of CENP-A for recruitment of inner kinetochore proteins, including stabilizing CENP-B binding to human centromeres or direct recruitment of CENP-C, respectively.engAdenoviridaeAutoantigensCentromereCentromere Protein BChromatinChromosomal Proteins, Non-HistoneEpithelial CellsGenetic VectorsHistonesHumansProtein Structure, TertiaryRetinaSchizosaccharomycesSchizosaccharomyces pombe ProteinsSignal TransductionEpigenesis, Geneticjournal article10.1038/ncb2805