Mis16 and Mis18 are required for CENP-A loading and histone deacetylation at centromeres.
Centromeres contain specialized chromatin that includes the centromere-specific histone H3 variant, spCENP-A/Cnp1. Here we report identification of five fission yeast centromere proteins, Mis14-18. Mis14 is recruited to kinetochores independently of CENP-A, and, conversely, CENP-A does not require Mis14 to associate with centromeres. In contrast, Mis15, Mis16 (strong similarity with human RbAp48 and RbAp46), Mis17, and Mis18 are all part of the CENP-A recruitment pathway. Mis15 and Mis17 form an evolutionarily conserved complex that also includes Mis6. Mis16 and Mis18 form a complex and maintain the deacetylated state of histones specifically in the central core of centromeres. Mis16 and Mis18 are the most upstream factors in kinetochore assembly as they can associate with kinetochores in all kinetochore mutants except for mis18 and mis16, respectively. RNAi knockdown in human cells shows that Mis16 function is conserved as RbAp48 and RbAp46 are both required for localization of human CENP-A.
Hayashi
Takeshi
T
Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Sakyo-ku, 606-8502, Japan.
Fujita
Yohta
Y
Iwasaki
Osamu
O
Adachi
Yoh
Y
Takahashi
Kohta
K
Yanagida
Mitsuhiro
M
D000107:Acetylation; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics; D002503:Centromere / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D034622:RNA Interference; D056505:Retinoblastoma-Binding Protein 4; D056524:Retinoblastoma-Binding Protein 7; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C410349:Cnp1 protein, S pombe; D006657:Histones; C107314:Mis6 protein, S pombe; D009687:Nuclear Proteins; C082637:RBBP4 protein, human; C490746:RBBP7 protein, human; C489969:Rbbp4 protein, mouse; D056505:Retinoblastoma-Binding Protein 4; D056524:Retinoblastoma-Binding Protein 7; D029702:Schizosaccharomyces pombe Proteins