title: 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.
authors.affiliation: Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093, USA.
authors.forename: Daniele
authors.initials: D
authors.lastname: Fachinetti
authors.forename: H Diego
authors.initials: HD
authors.lastname: Folco
authors.forename: Yael
authors.initials: Y
authors.lastname: Nechemia-Arbely
authors.forename: Luis P
authors.initials: LP
authors.lastname: Valente
authors.forename: Kristen
authors.initials: K
authors.lastname: Nguyen
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Wong
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Holland
authors.forename: Arshad
authors.initials: A
authors.lastname: Desai
authors.forename: Lars E T
authors.initials: LE
authors.lastname: Jansen
authors.forename: Don W
authors.initials: DW
authors.lastname: Cleveland
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D002503:Centromere / Q000502:physiology* / Q000648:ultrastructure; D000076247:Centromere Protein A; D051936:Centromere Protein B / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005822:Genetic Vectors; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017434:Protein Structure, Tertiary; D012160:Retina / Q000166:cytology / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D051936:Centromere Protein B; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D029702:Schizosaccharomyces pombe Proteins; C060905:centromere protein C