Crystal structure of the human centromeric nucleosome containing CENP-A

摘要: In eukaryotes, accurate chromosome segregation during mitosis and meiosis is coordinated by kinetochores, which are unique chromosomal sites for microtubule attachment. Centromeres specify the kinetochore formation on individual chromosomes, epigenetically marked assembly of nucleosomes containing centromere-specific histone H3 variant, CENP-A. Although underlying mechanism unclear, centromere inheritance probably dictated architecture centromeric nucleosome. Here we report crystal structure human nucleosome CENP-A its cognate α-satellite DNA derivative (147 base pairs). nucleosome, wrapped around octamer, consisting two each histones H2A, H2B, H4 CENP-A, in a left-handed orientation. However, unlike canonical only central 121 pairs visible. The thirteen from both ends invisible structure, αN helix shorter than that H3, known to be important orientation A structural comparison revealed contains extra amino acid residues (Arg 80 Gly 81) loop 1 region, completely exposed solvent. Mutations reduced retention at centromeres cells. Therefore, may function stabilizing chromatin possibly providing binding site trans-acting factors. provides first atomic-resolution picture