A two-step mechanism for epigenetic specification of centromere identity and function

The 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.

Keywords

Adenoviridae Autoantigens Centromere Centromere Protein B Chromatin Chromosomal Proteins, Non-Histone Epithelial Cells Genetic Vectors Histones Humans Protein Structure, Tertiary Retina Schizosaccharomyces Schizosaccharomyces pombe Proteins Signal Transduction Epigenesis, Genetic

URI

http://hdl.handle.net/10400.7/625

Citation

Fachinetti, 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.