title: Heterochromatin and RNAi are required to establish CENP-A chromatin at centromeres.
abstract: Heterochromatin is defined by distinct posttranslational modifications on histones, such as methylation of histone H3 at lysine 9 (H3K9), which allows heterochromatin protein 1 (HP1)-related chromodomain proteins to bind. Heterochromatin is frequently found near CENP-A chromatin, which is the key determinant of kinetochore assembly. We have discovered that the RNA interference (RNAi)-directed heterochromatin flanking the central kinetochore domain at fission yeast centromeres is required to promote CENP-A(Cnp1) and kinetochore assembly over the central domain. The H3K9 methyltransferase Clr4 (Suv39); the ribonuclease Dicer, which cleaves heterochromatic double-stranded RNA to small interfering RNA (siRNA); Chp1, a component of the RNAi effector complex (RNA-induced initiation of transcriptional gene silencing; RITS); and Swi6 (HP1) are required to establish CENP-A(Cnp1) chromatin on naïve templates. Once assembled, CENP-A(Cnp1) chromatin is propagated by epigenetic means in the absence of heterochromatin. Thus, another, potentially conserved, role for centromeric RNAi-directed heterochromatin has been identified.
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, 6.34 Swann Building, Edinburgh EH9 3JR, Scotland, UK.
authors.forename: Hernan Diego
authors.initials: HD
authors.lastname: Folco
authors.forename: Alison L
authors.initials: AL
authors.lastname: Pidoux
authors.forename: Takeshi
authors.initials: T
authors.lastname: Urano
authors.forename: Robin C
authors.initials: RC
authors.lastname: Allshire
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002503:Centromere / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D006570:Heterochromatin / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase; D018386:Kinetochores / Q000378:metabolism; D008780:Methyltransferases / Q000378:metabolism; D034622:RNA Interference; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D014170:Transformation, Genetic
chemical_list: D018797:Cell Cycle Proteins; C115018:Chp1 protein, S pombe; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C410349:Cnp1 protein, S pombe; D004271:DNA, Fungal; D006570:Heterochromatin; D012331:RNA, Fungal; D034741:RNA, Small Interfering; D029702:Schizosaccharomyces pombe Proteins; C465958:Swi6 protein, S pombe; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C112744:clr4 protein, S pombe; D043244:Ribonuclease III