RRC ID 46101
著者 Gu SG, Pak J, Guang S, Maniar JM, Kennedy S, Fire A.
タイトル Amplification of siRNA in Caenorhabditis elegans generates a transgenerational sequence-targeted histone H3 lysine 9 methylation footprint.
ジャーナル Nat Genet
Abstract 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.
巻・号 44(2)
ページ 157-64
公開日 2012-1-8
DOI 10.1038/ng.1039
PII ng.1039
PMID 22231482
PMC PMC3848608
MeSH Animals Base Sequence Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Chromatin / metabolism Gene Expression Profiling Genetic Loci Histones / metabolism* Lysine / metabolism* Methylation Molecular Sequence Data RNA, Double-Stranded / pharmacology RNA, Small Interfering / metabolism* Sequence Analysis, DNA
IF 27.605
引用数 142
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm914 tm1195 tm894 tm1019 tm887 tm1144