Priming of centromere for CENP-A recruitment by human hMis18alpha, hMis18beta, and M18BP1.
The centromere is the chromosomal site that joins to microtubules during mitosis for proper segregation. Determining the location of a centromere-specific histone H3 called CENP-A at the centromere is vital for understanding centromere structure and function. Here, we report the identification of three human proteins essential for centromere/kinetochore structure and function, hMis18alpha, hMis18beta, and M18BP1, the complex of which is accumulated specifically at the telophase-G1 centromere. We provide evidence that such centromeric localization of hMis18 is essential for the subsequent recruitment of de novo-synthesized CENP-A. If any of the three is knocked down by RNAi, centromere recruitment of newly synthesized CENP-A is rapidly abolished, followed by defects such as misaligned chromosomes, anaphase missegregation, and interphase micronuclei. Tricostatin A, an inhibitor to histone deacetylase, suppresses the loss of CENP-A recruitment to centromeres in hMis18alpha RNAi cells. Telophase centromere chromatin may be primed or licensed by the hMis18 complex and RbAp46/48 to recruit CENP-A through regulating the acetylation status in the centromere.
Fujita
Yohta
Y
CREST Research Project of Japan Science and Technology Corporation (JST), Graduate School of Biostudies, Kyoto University, Yoshida-Honmachi, Kyoto 606-8501, Japan.
Hayashi
Takeshi
T
Kiyomitsu
Tomomi
T
Toyoda
Yusuke
Y
Kokubu
Aya
A
Obuse
Chikashi
C
Yanagida
Mitsuhiro
M
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002503:Centromere / Q000187:drug effects / Q000378:metabolism*; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism*; D020090:Chromosome Segregation / Q000187:drug effects; D016384:Consensus Sequence; D015894:Genome, Human / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008677:Metaphase / Q000187:drug effects; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D013692:Telophase / Q000187:drug effects; D014714:Vertebrates
D048868:Adaptor Proteins, Signal Transducing; D001324:Autoantigens; C000619700:CENPA protein, human; D018797:Cell Cycle Proteins; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D006877:Hydroxamic Acids; C502942:MIS18A protein, human; C517147:MIS18BP1 protein, human; C517146:OIP5 protein, human; D020598:Proto-Oncogene Proteins c-myb; D011993:Recombinant Fusion Proteins; D029702:Schizosaccharomyces pombe Proteins; C012589:trichostatin A