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

作者：Fachinetti Daniele; Folco H Diego; Nechemia Arbely Yael; Valente Luis P; Nguyen Kristen; Wong Alex J; Zhu Quan; Holland Andrew J; Desai Arshad; Jansen Lars E T; Cleveland Don W^*

来源：Nature Cell Biology, 2013, 15(9): 1056-+.

DOI：10.1038/ncb2805

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.

• 出版日期2013-9