Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi.
Eukaryotic heterochromatin is characterized by a high density of repeats and transposons, as well as by modified histones, and influences both gene expression and chromosome segregation. In the fission yeast Schizosaccharomyces pombe, we deleted the argonaute, dicer, and RNA-dependent RNA polymerase gene homologs, which encode part of the machinery responsible for RNA interference (RNAi). Deletion results in the aberrant accumulation of complementary transcripts from centromeric heterochromatic repeats. This is accompanied by transcriptional de-repression of transgenes integrated at the centromere, loss of histone H3 lysine-9 methylation, and impairment of centromere function. We propose that double-stranded RNA arising from centromeric repeats targets formation and maintenance of heterochromatin through RNAi.
Cold Spring Harbor Laboratory, Watson School of Biological Sciences, Cold Spring Harbor, NY 11724, USA.
Thomas A
TA
Volpe
Catherine
C
Kidner
Ira M
IM
Hall
Grace
G
Teng
Shiv I S
SI
Grewal
Robert A
RA
Martienssen
D002503:Centromere / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D019175:DNA Methylation; D004251:DNA Transposable Elements; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D020868:Gene Silencing; D005800:Genes, Fungal; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008957:Models, Genetic; D012330:RNA, Double-Stranded / Q000378:metabolism; D012331:RNA, Fungal / Q000378:metabolism; D034741:RNA, Small Interfering; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D043244:Ribonuclease III; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D019076:Transgenes
D002868:Chromosomal Proteins, Non-Histone; D004251:DNA Transposable Elements; D006570:Heterochromatin; D006657:Histones; D012330:RNA, Double-Stranded; D012331:RNA, Fungal; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D029702:Schizosaccharomyces pombe Proteins; C465958:Swi6 protein, S pombe; D012324:RNA-Dependent RNA Polymerase; D004722:Endoribonucleases; D043244:Ribonuclease III; D008239:Lysine