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Nat Cell Biol. 2013 Sep;15(9):1056-66. doi: 10.1038/ncb2805. Epub 2013 Jul 21.

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

Author information

1
Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093, USA.

Abstract

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.

Comment in

PMID:
23873148
PMCID:
PMC4418506
DOI:
10.1038/ncb2805
[Indexed for MEDLINE]
Free PMC Article

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