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

Daniele Fachinetti, H. Diego Folco, Yael Nechemia-Arbely, Luis P. Valente, Kristen Nguyen, Alex J. Wong, Quan Zhu, Andrew J. Holland, Arshad Desai, Lars E.T. Jansen, Don W. Cleveland

Research output: Contribution to journalArticlepeer-review

155 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1056-1066
Number of pages11
JournalNature cell biology
Issue number9
StatePublished - Sep 2013

ASJC Scopus subject areas

  • Cell Biology


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