論文 - 詳細
RRC ID | 51336 |
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著者 | Kalinava N, Ni JZ, Peterman K, Chen E, Gu SG. |
タイトル | Decoupling the downstream effects of germline nuclear RNAi reveals that H3K9me3 is dispensable for heritable RNAi and the maintenance of endogenous siRNA-mediated transcriptional silencing in Caenorhabditis elegans. |
ジャーナル | Epigenetics Chromatin |
Abstract |
BACKGROUND:Germline nuclear RNAi in C. elegans is a transgenerational gene-silencing pathway that leads to H3K9 trimethylation (H3K9me3) and transcriptional silencing at the target genes. H3K9me3 induced by either exogenous double-stranded RNA (dsRNA) or endogenous siRNA (endo-siRNA) is highly specific to the target loci and transgenerationally heritable. Despite these features, the role of H3K9me3 in siRNA-mediated transcriptional silencing and inheritance of the silencing state at native target genes is unclear. In this study, we took combined genetic and whole-genome approaches to address this question. RESULTS:Here we demonstrate that siRNA-mediated H3K9me3 requires combined activities of three H3K9 histone methyltransferases: MET-2, SET-25, and SET-32. set-32 single, met-2 set-25 double, and met-2 set-25;set-32 triple mutant adult animals all exhibit prominent reductions in H3K9me3 throughout the genome, with met-2 set-25;set-32 mutant worms losing all detectable H3K9me3 signals. Surprisingly, loss of high-magnitude H3K9me3 at the native nuclear RNAi targets has no effect on the transcriptional silencing state. In addition, the exogenous dsRNA-induced transcriptional silencing and heritable RNAi at oma-1, a well-established nuclear RNAi reporter gene, are completely resistant to the loss of H3K9me3. CONCLUSIONS:Nuclear RNAi-mediated H3K9me3 in C. elegans requires multiple histone methyltransferases, including MET-2, SET-25, and SET-32. H3K9me3 is not essential for dsRNA-induced heritable RNAi or the maintenance of endo-siRNA-mediated transcriptional silencing in C. elegans. We propose that siRNA-mediated transcriptional silencing in C. elegans can be maintained by an H3K9me3-independent mechanism. |
巻・号 | 10 |
ページ | 6 |
公開日 | 2017-2-15 |
DOI | 10.1186/s13072-017-0114-8 |
PII | 114 |
PMID | 28228846 |
PMC | PMC5311726 |
MeSH | Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / antagonists & inhibitors Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / antagonists & inhibitors Carrier Proteins / genetics Carrier Proteins / metabolism Chromatin Immunoprecipitation Genome Genomic Instability Germ Cells / metabolism High-Throughput Nucleotide Sequencing Histone Methyltransferases Histone-Lysine N-Methyltransferase / genetics Histone-Lysine N-Methyltransferase / metabolism Histones / genetics Histones / metabolism* Methylation Microscopy, Fluorescence Mutagenesis RNA Interference* RNA, Double-Stranded / metabolism RNA, Messenger / metabolism RNA, Small Interfering / metabolism* Real-Time Polymerase Chain Reaction Sequence Analysis, RNA Transcription, Genetic |
IF | 4.237 |
引用数 | 26 |
リソース情報 | |
線虫 | tm1200 tm3526 |