title: Cell-cycle-dependent structural transitions in the human CENP-A nucleosome in vivo.
abstract: In eukaryotes, DNA is packaged into chromatin by canonical histone proteins. The specialized histone H3 variant CENP-A provides an epigenetic and structural basis for chromosome segregation by replacing H3 at centromeres. Unlike exclusively octameric canonical H3 nucleosomes, CENP-A nucleosomes have been shown to exist as octamers, hexamers, and tetramers. An intriguing possibility reconciling these observations is that CENP-A nucleosomes cycle between octamers and tetramers in vivo. We tested this hypothesis by tracking CENP-A nucleosomal components, structure, chromatin folding, and covalent modifications across the human cell cycle. We report that CENP-A nucleosomes alter from tetramers to octamers before replication and revert to tetramers after replication. These structural transitions are accompanied by reversible chaperone binding, chromatin fiber folding changes, and previously undescribed modifications within the histone fold domains of CENP-A and H4. Our results reveal a cyclical nature to CENP-A nucleosome structure and have implications for the maintenance of epigenetic memory after centromere replication.
authors: Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors: Minh
authors: M
authors: Bui
authors: Emilios K
authors: EK
authors: Dimitriadis
authors: Christian
authors: C
authors: Hoischen
authors: Eunkyung
authors: E
authors: An
authors: Delphine
authors: D
authors: Quénet
authors: Sindy
authors: S
authors: Giebe
authors: Aleksandra
authors: A
authors: Nita-Lazar
authors: Stephan
authors: S
authors: Diekmann
authors: Yamini
authors: Y
authors: Dalal
mesh_terms: D001324:Autoantigens / Q000737:chemistry / Q000378:metabolism*; D002453:Cell Cycle; D002503:Centromere / Q000378:metabolism; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009707:Nucleosomes / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C524371:HJURP protein, human; D006657:Histones; D009707:Nucleosomes