Science · 2002 · 2.1K citations · 56 references
Life SciencesGeneticsMolecular GeneticsChromatin BiologyGene ExpressionTranscriptional RegulationChromatinGene SilencingHistone ModificationsHistone ProteinsRna InterferenceTranscriptional SilencingCentromere RepeatsHeterochromatin MaintenanceHeterochromatin RegulationHistone Methylation At Lysine 9Histone-lysine MethylationTranscriptional Gene SilencingTranscriptional RepressionYeast Chromosome Segregation
Eukaryotic heterochromatin, rich in repeats and transposons and marked by modified histones, regulates gene expression and chromosome segregation. The study proposes that centromeric repeat‑derived double‑stranded RNA directs heterochromatin formation and maintenance via RNAi. The authors deleted argonaute, dicer, and RNA‑dependent RNA polymerase genes in Schizosaccharomyces pombe to disrupt RNAi and assess its role in heterochromatin. Loss of RNAi components caused accumulation of centromeric transcripts, derepression of centromere‑integrated transgenes, loss of H3K9 methylation, and impaired centromere function.
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.
56
Role for a bidentate ribonuclease in the initiation step of RNA interference
Emily Bernstein, Amy A. Caudy, Scott M. Hammond et al. · Nature · 2001 · 4.9K citations
An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells
Scott M. Hammond, Emily Bernstein, David Beach et al. · Nature · 2000 · 3K citations
Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain
Andrew J. Bannister, Philip Zegerman, Janet F. Partridge et al. · Nature · 2001 · 2.9K citations
Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins
Monika Lachner, Dónal O’Carroll, Stephen Rea et al. · Nature · 2001 · 2.8K citations
Regulation of chromatin structure by site-specific histone H3 methyltransferases
Stephen Rea, Frank Eisenhaber, Dónal O’Carroll et al. · Nature · 2000 · 2.8K citations