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

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.

SUBMITTER: Fachinetti D

PROVIDER: S-EPMC4418506 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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

Fachinetti Daniele D Folco H Diego HD Nechemia-Arbely Yael Y Valente Luis P LP Nguyen Kristen K Wong Alex J AJ Zhu Quan Q Holland Andrew J AJ Desai Arshad A Jansen Lars E T LE Cleveland Don W DW

Nature cell biology 20130721 9

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- ...[more]

PMID: 23873148

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DNA replication acts as an error correction mechanism to maintain centromere identity by restricting CENP-A to centromeres.

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