title: An epigenetic mark generated by the incorporation of CENP-A into centromeric nucleosomes.
abstract: Mammalian centromeres are defined epigenetically. Although the physical nature of the epigenetic mark is unknown, nucleosomes in which CENP-A replaces histone H3 are at the foundation of centromeric chromatin. Hydrogen/deuterium exchange MS is now used to show that assembly into nucleosomes imposes stringent conformational constraints, reducing solvent accessibility in almost all histone regions by >3 orders of magnitude. Despite this, nucleosomes assembled with CENP-A are substantially more conformationally rigid than those assembled with histone H3 independent of DNA template. Substitution of the CENP-A centromere targeting domain into histone H3 to convert it into a centromere-targeted histone that can functionally replace CENP-A in centromere maintenance generates the same more rigid nucleosome, as does CENP-A. Thus, the targeting information directing CENP-A deposition at the centromere produces a structurally distinct nucleosome, supporting a CENP-A-driven self-assembly mechanism that mediates maintenance of centromere identity.
authors.affiliation: Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Ben E
authors.initials: BE
authors.lastname: Black
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Brock
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bédard
authors.forename: Virgil L
authors.initials: VL
authors.lastname: Woods
authors.forename: Don W
authors.initials: DW
authors.lastname: Cleveland
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism*; D003903:Deuterium; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D006859:Hydrogen; D008968:Molecular Conformation; D009707:Nucleosomes / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D001324:Autoantigens; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D009707:Nucleosomes; D006859:Hydrogen; D003903:Deuterium