title: CENP-C directs a structural transition of CENP-A nucleosomes mainly through sliding of DNA gyres.
abstract: The histone H3 variant CENP-A is incorporated into nucleosomes that mark centromere location. We have recently reported that CENP-A nucleosomes, compared with their H3 counterparts, confer an altered nucleosome shape. Here, using a single-molecule fluorescence resonance energy transfer (FRET) approach with recombinant human histones and centromere DNA, we found that the nucleosome shape change directed by CENP-A is dominated by lateral passing of two DNA gyres (gyre sliding). A nonhistone centromere protein, CENP-C, binds and reshapes the nucleosome, sliding the DNA gyres back to positions similar to those in canonical nucleosomes containing conventional histone H3. The model that we generated to explain the CENP-A-nucleosome transition provides an example of a shape change imposed by external binding proteins and has notable implications for understanding of the epigenetic basis of the faithful inheritance of centromere location on chromosomes.
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Falk
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Jaehyoun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Nikolina
authors.initials: N
authors.lastname: Sekulic
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Sennett
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Tae-Hee
authors.initials: TH
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Ben E
authors.initials: BE
authors.lastname: Black
mesh_terms: D001324:Autoantigens / Q000378:metabolism*; D002503:Centromere / Q000737:chemistry* / Q000378:metabolism*; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D009707:Nucleosomes; C060905:centromere protein C