CENP-B controls centromere formation depending on the chromatin context.
The centromere is a chromatin region that serves as the spindle attachment point and directs accurate inheritance of eukaryotic chromosomes during cell divisions. However, the mechanism by which the centromere assembles and stabilizes at a specific genomic region is not clear. The de novo formation of a human/mammalian artificial chromosome (HAC/MAC) with a functional centromere assembly requires the presence of alpha-satellite DNA containing binding motifs for the centromeric CENP-B protein. We demonstrate here that de novo centromere assembly on HAC/MAC is dependent on CENP-B. In contrast, centromere formation is suppressed in cells expressing CENP-B when alpha-satellite DNA was integrated into a chromosomal site. Remarkably, on those integration sites CENP-B enhances histone H3-K9 trimethylation and DNA methylation, thereby stimulating heterochromatin formation. Thus, we propose that CENP-B plays a dual role in centromere formation, ensuring de novo formation on DNA lacking a functional centromere but preventing the formation of excess centromeres on chromosomes.
Okada
Teruaki
T
Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.
Ohzeki
Jun-ichirou
J
Nakano
Megumi
M
Yoda
Kinya
K
Brinkley
William R
WR
Larionov
Vladimir
V
Masumoto
Hiroshi
H
D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A; D051936:Centromere Protein B / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D022222:Chromosomes, Artificial, Human / Q000378:metabolism*; D022221:Chromosomes, Artificial, Mammalian / Q000378:metabolism*; D018899:CpG Islands; D019175:DNA Methylation; D004276:DNA, Satellite / Q000378:metabolism*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000378:metabolism*; D006570:Heterochromatin / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D013997:Time Factors; D014162:Transfection
D001324:Autoantigens; D000076247:Centromere Protein A; D051936:Centromere Protein B; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004276:DNA, Satellite; D006570:Heterochromatin; D006657:Histones; D008239:Lysine