| Citation | Esse R, Gushchanskaia ES, Lord A, Grishok A. DOT1L complex suppresses transcription from enhancer elements and ectopic RNAi in Caenorhabditis elegans. RNA, 2019. |
| PubMed ID | 31300558 |
| Short Description | DOT1L complex suppresses transcription from enhancer elements and ectopic RNAi in Caenorhabditis elegans. GEO Record: GSE115677 Platform: GPL19230 Download gene-centric, log2 transformed data: WBPaper00057029.ce.mr.csv |
| # of Conditions | 12 |
Full Description
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Methylation of histone H3 on lysine 79 (H3K79) by DOT1L is associated with actively transcribed genes. Earlier, we described that DOT-1.1, the Caenorhabditis elegans homologue of mammalian DOT1L, cooperates with the chromatin-binding protein ZFP-1 (AF10 homologue) to negatively modulate transcription of highly and widely expressed target genes. Also, reduction of ZFP-1 levels has consistently been associated with lower efficiency of RNA interference (RNAi) triggered by exogenous double-stranded RNA (dsRNA), but the reason for this is not clear. Here, we demonstrate that the DOT1L complex suppresses transcription originating from enhancer elements and antisense transcription, thus potentiating expression of enhancer-regulated genes. We also show that worms lacking H3K79 methylation do not survive and this lethality is suppressed by mutations in caspase-3, and Dicer complex components that initiate gene silencing response to exogenous dsRNA. Our results suggest that ectopic elevation of endogenous dsRNA directly or indirectly resulting from global misregulation of transcription in DOT1L complex mutants may engage the Dicer complex and, therefore, limit the efficiency of exogenous RNAi. Experimental Details: WBPaper00057029:N2_rep1 WBPaper00057029:N2_rep2 WBPaper00057029:N2_rep3 WBPaper00057029:zfp-1(ok554)_rep1 WBPaper00057029:zfp-1(ok554)_rep2 WBPaper00057029:zfp-1(ok554)_rep3 WBPaper00057029:dot-1.1(gk1050594)_rep1 WBPaper00057029:dot-1.1(gk1050594)_rep2 WBPaper00057029:dot-1.1(gk1050594)_rep3 WBPaper00057029:mml-1(gk402844)_rep1 WBPaper00057029:mml-1(gk402844)_rep2 WBPaper00057029:mml-1(gk402844)_rep3. |
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