title: Formation of a centromere-specific chromatin structure.
abstract: The kinetochore is formed on centromeric DNA as a key interface with microtubules from the mitotic spindle to achieve accurate chromosome segregation during mitosis. However, in contrast to other regions of the chromosome, the position of the kinetochore is specified by sequence-independent epigenetic mechanisms. Most recent work on kinetochore specification has focused on the centromere-specific histone H3-variant CENP-A. Whereas CENP-A is an important epigenetic marker for the kinetochore specification, it is unclear how centromeric chromatin structure is organized. To understand centromeric chromatin structure, we focused on additional centromere proteins that have an intrinsic DNA binding activity and identified the DNA binding CENP-T-W-S-X complex. Tetramer formation of CENP-T-W-S-X is essential for functional kinetochore assembly in vertebrate cells. Our structural and biochemical analysis reveals that the CENP-T-W-S-X complex is composed of four histone-fold domains with structural similarity to nucleosomes and displays DNA supercoiling activity. These results suggest that the CENP-T-W-S-X complex forms a unique nucleosome-like structure at centromeric chromatin. In addition, CENP-S and CENP-X function at non-centromeric sites. The intriguing histone-like properties of these proteins suggest that they may form nucleosome-like structures at various genome loci, extending the chromatin code beyond classical histone variants.
authors.affiliation: Department of Molecular Genetics, National Institute of Genetics, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Japan. tfukagaw@lab.nig.ac.jp
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Fukagawa
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D000076247:Centromere Protein A; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004278:DNA, Superhelical / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000737:chemistry* / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004278:DNA, Superhelical; D004268:DNA-Binding Proteins; D006657:Histones; D009707:Nucleosomes