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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Autoantigens / genetics*
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Autoantigens / metabolism
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Centromere / physiology*
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Centromere / ultrastructure
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Centromere Protein A
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Centromere Protein B / genetics
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Centromere Protein B / metabolism
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Chromatin / genetics
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Chromatin / metabolism
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Chromosomal Proteins, Non-Histone / genetics*
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Chromosomal Proteins, Non-Histone / metabolism
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Chromosomal Proteins, Non-Histone / ultrastructure
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Epigenesis, Genetic*
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Epithelial Cells / cytology
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Epithelial Cells / metabolism
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Genetic Vectors
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Histones / genetics*
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Histones / metabolism
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Humans
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Protein Structure, Tertiary
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Retina / cytology
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Retina / metabolism
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Schizosaccharomyces / cytology
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Schizosaccharomyces / genetics*
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Schizosaccharomyces / metabolism
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Schizosaccharomyces pombe Proteins / genetics*
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Schizosaccharomyces pombe Proteins / metabolism
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Signal Transduction
Substances
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Autoantigens
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CENPA protein, human
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Centromere Protein A
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Centromere Protein B
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Chromatin
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Chromosomal Proteins, Non-Histone
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Histones
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Schizosaccharomyces pombe Proteins
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centromere protein C