Amplification of siRNA in Caenorhabditis elegans generates a transgenerational sequence-targeted histone H3 lysine 9 methylation footprint.
Exogenous double-stranded RNA (dsRNA) has been shown to exert homology-dependent effects at the level of both target mRNA stability and chromatin structure. Using C. elegans undergoing RNAi as an animal model, we have investigated the generality, scope and longevity of dsRNA-targeted chromatin effects and their dependence on components of the RNAi machinery. Using high-resolution genome-wide chromatin profiling, we found that a diverse set of genes can be induced to acquire locus-specific enrichment of histone H3 lysine 9 trimethylation (H3K9me3), with modification footprints extending several kilobases from the site of dsRNA homology and with locus specificity sufficient to distinguish the targeted locus from the other 20,000 genes in the C. elegans genome. Genetic analysis of the response indicated that factors responsible for secondary siRNA production during RNAi were required for effective targeting of chromatin. Temporal analysis revealed that H3K9me3, once triggered by dsRNA, can be maintained in the absence of dsRNA for at least two generations before being lost. These results implicate dsRNA-triggered chromatin modification in C. elegans as a programmable and locus-specific response defining a metastable state that can persist through generational boundaries.
Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
Sam Guoping
SG
Gu
Julia
J
Pak
Shouhong
S
Guang
Jay M
JM
Maniar
Scott
S
Kennedy
Andrew
A
Fire
D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D020869:Gene Expression Profiling; D056426:Genetic Loci; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008969:Molecular Sequence Data; D012330:RNA, Double-Stranded / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism*; D017422:Sequence Analysis, DNA
D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D006657:Histones; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D008239:Lysine