title: CENP-A arrays are more condensed than canonical arrays at low ionic strength.
abstract: The centromeric histone H3 variant centromeric protein A (CENP-A), whose sequence is the least conserved among all histone variants, is responsible for specifying the location of the centromere. Here, we present a comprehensive study of CENP-A nucleosome arrays by cryo-electron tomography. We see that CENP-A arrays have different biophysical properties than canonical ones under low ionic conditions, as they are more condensed with a 20% smaller average nearest-neighbor distance and a 30% higher nucleosome density. We find that CENP-A nucleosomes have a predominantly crossed DNA entry/exit site that is narrowed on average by 8°, and they have a propensity to stack face to face. We therefore propose that CENP-A induces geometric constraints at the nucleosome DNA entry/exit site to bring neighboring nucleosomes into close proximity. This specific property of CENP-A may be responsible for generating a fundamental process that contributes to increased chromatin fiber compaction that is propagated under physiological conditions to form centromeric chromatin.
authors.affiliation: Buchmann Institute for Molecular Life Sciences, Frankfurt, Germany.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Geiss
authors.affiliation: Buchmann Institute for Molecular Life Sciences, Frankfurt, Germany.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Keramisanou
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Nikolina
authors.initials: N
authors.lastname: Sekulic
authors.affiliation: Buchmann Institute for Molecular Life Sciences, Frankfurt, Germany.
authors.forename: Margot P
authors.initials: MP
authors.lastname: Scheffer
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ben E
authors.initials: BE
authors.lastname: Black
authors.affiliation: Buchmann Institute for Molecular Life Sciences, Frankfurt, Germany. Electronic address: achilleas.frangakis@biophysik.org.
authors.forename: Achilleas S
authors.initials: AS
authors.lastname: Frangakis
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000737:chemistry* / Q000378:metabolism; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009707:Nucleosomes / Q000737:chemistry / Q000648:ultrastructure*; D009994:Osmolar Concentration; D011487:Protein Conformation; D014982:Xenopus laevis
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D009707:Nucleosomes; D004247:DNA