Centromere-specific assembly of CENP-a nucleosomes is mediated by HJURP.
The centromere is responsible for accurate chromosome segregation. Mammalian centromeres are specified epigenetically, with all active centromeres containing centromere-specific chromatin in which CENP-A replaces histone H3 within the nucleosome. The proteins responsible for assembly of human CENP-A into centromeric nucleosomes during the G1 phase of the cell cycle are shown here to be distinct from the chromatin assembly factors previously shown to load other histone H3 variants. Here we demonstrate that prenucleosomal CENP-A is complexed with histone H4, nucleophosmin 1, and HJURP. Recruitment of new CENP-A into nucleosomes at replicated centromeres is dependent on HJURP. Recognition by HJURP is mediated through the centromere targeting domain (CATD) of CENP-A, a region that we demonstrated previously to induce a unique conformational rigidity to both the subnucleosomal CENP-A heterotetramer and the corresponding assembled nucleosome. We propose HJURP to be a cell-cycle-regulated CENP-A-specific histone chaperone required for centromeric chromatin assembly.
Ludwig Institute for Cancer Research, La Jolla, CA 92093-0670, USA. dfoltz@virginia.edu
Daniel R
DR
Foltz
Lars E T
LE
Jansen
Aaron O
AO
Bailey
John R
JR
Yates
Emily A
EA
Bassett
Stacey
S
Wood
Ben E
BE
Black
Don W
DW
Cleveland
D001324:Autoantigens / Q000378:metabolism*; D002460:Cell Line; D002503:Centromere / Q000378:metabolism* / Q000648:ultrastructure; D000076247:Centromere Protein A; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016193:G1 Phase; D006657:Histones / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D000090243:Nucleophosmin; D009707:Nucleosomes / Q000378:metabolism* / Q000648:ultrastructure
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; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D009707:Nucleosomes; D000090243:Nucleophosmin