Caenorhabditis elegans nuclear RNAi factor SET-32 deposits the transgenerational histone modification, H3K23me3

Schwartz-Orbach, Lianna; Zhang, Chenzhen; Amin, Richa; Kaur, Diljeet; Zhebrun, Anna; Ni, Julie Zhouli; Gu, Sam Guoping

doi:10.7554/elife.54309

Cited by 43 publications

(36 citation statements)

References 59 publications

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“…HRDE-1-bound small RNAs can recognize nascent transcripts and recruit chromatin modifiers to establish repressive histone modifications (e.g., H3K9me3) at target genes 22,40 . Neither the histone methyltransferases MET-2 41,42 or SET-32 42,43 nor the chromodomain protein HERI-1 44 was required for silencing (Fig. 3c).…”

Section: Resultsmentioning

confidence: 98%

Mating can initiate stable RNA silencing that overcomes epigenetic recovery

et al. 2021

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Stable epigenetic changes appear uncommon, suggesting that changes typically dissipate or are repaired. Changes that stably alter gene expression across generations presumably require particular conditions that are currently unknown. Here we report that a minimal combination of cis-regulatory sequences can support permanent RNA silencing of a single-copy transgene and its derivatives in C. elegans simply upon mating. Mating disrupts competing RNA-based mechanisms to initiate silencing that can last for >300 generations. This stable silencing requires components of the small RNA pathway and can silence homologous sequences in trans. While animals do not recover from mating-induced silencing, they often recover from and become resistant to trans silencing. Recovery is also observed in most cases when double-stranded RNA is used to silence the same coding sequence in different regulatory contexts that drive germline expression. Therefore, we propose that regulatory features can evolve to oppose permanent and potentially maladaptive responses to transient change.

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Section: Resultsmentioning

confidence: 98%

Mating can initiate stable RNA silencing that overcomes epigenetic recovery

et al. 2021

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“…We also observed that deficiency for SET-32, an H3K23 methyltransferase that promotes transgenerational silencing responses to small RNAs, results in progeny with very low levels of Pot1 foci (Fig. 3b , ANOVA p < 10 −8 ) 47 , 50 , 51 .…”

Section: Resultsmentioning

confidence: 61%

“…Although the absence of MET-2 and SET-25 together abolishes all germline H3K9 methylation 47 , we found that these proteins are independently required to promote the stability of Pot1 foci. A third histone methyltransferase that is required for Pot1 focus formation, SET-32, methylates H3K23, which is a heterochromatic mark that has been recently identified in C. elegans 51 , 68 . SET-25 and SET-32 have previously been shown to respond to small RNAs by establishing silent chromosome domains that are then maintained for multiple generations 69 .…”

Section: Discussionmentioning

confidence: 99%

Gametes deficient for Pot1 telomere binding proteins alter levels of telomeric foci for multiple generations

et al. 2021

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Deficiency for telomerase results in transgenerational shortening of telomeres. However, telomeres have no known role in transgenerational epigenetic inheritance. C. elegans Protection Of Telomeres 1 (Pot1) proteins form foci at the telomeres of germ cells that disappear at fertilization and gradually accumulate during development. We find that gametes from mutants deficient for Pot1 proteins alter levels of telomeric foci for multiple generations. Gametes from pot-2 mutants give rise to progeny with abundant POT-1::mCherry and mNeonGreen::POT-2 foci throughout development, which persists for six generations. In contrast, gametes from pot-1 mutants or pot-1; pot-2 double mutants induce diminished Pot1 foci for several generations. Deficiency for MET-2, SET-25, or SET-32 methyltransferases, which promote heterochromatin formation, results in gametes that induce diminished Pot1 foci for several generations. We propose that C. elegans POT-1 may interact with H3K9 methyltransferases during pot-2 mutant gametogenesis to induce a persistent form of transgenerational epigenetic inheritance that causes constitutively high levels of heterochromatic Pot1 foci.

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“…Small-RNA-guided chromatin modifications have been widely studied in many organisms. In C. elegan s, NRDE complex transports 22G RNAs from the cytoplasm to the nucleus, induces H3K9, H3K23 and H3K27 trimethylation and mediates transgenerational inheritance of RNAi [25, 34]. In this study, we found that the risiRNA/NRDE complex inhibits RNAP I transcription without altering the status of H3K9 and H3K27 trimethylation of rDNA genes.…”

Section: Discussionmentioning

confidence: 67%

“…We further investigated the molecular mechanism of nucleolar RNAi. Small interference RNAs guide the NRDE complex to targeted pre-mRNAs, induce H3K9, H3K23 and H3K27 trimethylation at the corresponding genomic loci, inhibit RNAP II-mediated transcription elongation, and silence gene expression in the nucleus in C. elegans [19, 20, 24, 25]. To determine whether risiRNAs induce histone modifications, we conducted ChIP assays with anti-H3K9me3 and anti-H3K27me3 antibodies.…”

Section: Resultsmentioning

confidence: 99%

Co-surveillance of ribosomal RNA by the exosome complex and nucleolar RNAi inC. elegans

Liao

Chen

et al. 2020

Preprint

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Eukaryotic cells express a wide variety of endogenous small regulatory RNAs that function in the nucleus. We previously found that erroneous rRNAs induce the generation of antisense ribosomal siRNAs (risiRNAs) which silence the expression of rRNAs via the nuclear RNAi defective (Nrde) pathway. To further understand the biological roles and mechanisms of this class of small regulatory RNAs, we conducted forward genetic screening to identify factors involved in risiRNA generation in Caenorhabditis elegans. We found that risiRNAs accumulated in the RNA exosome mutants. risiRNAs directed a NRDE-dependent silencing of pre-rRNAs in the nucleolus. In the presence of risiRNA, NRDE-2 accumulated in the nucleolus and colocalized with RNA polymerase I. risiRNA inhibited the transcription elongation of RNA polymerase I by decreasing RNAP I occupancy downstream of the site of RNAi. Meanwhile, exosome mislocalized from the nucleolus to nucleoplasm in suppressor of siRNA (susi) mutants, in which erroneous rRNAs accumulated. These results establish a novel model of rRNA surveillance by combining ribonuclease-mediated RNA degradation with small RNA-directed nucleolar RNAi system.

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Caenorhabditis elegans nuclear RNAi factor SET-32 deposits the transgenerational histone modification, H3K23me3

Cited by 43 publications

References 59 publications

Mating can initiate stable RNA silencing that overcomes epigenetic recovery

Mating can initiate stable RNA silencing that overcomes epigenetic recovery

Gametes deficient for Pot1 telomere binding proteins alter levels of telomeric foci for multiple generations

Co-surveillance of ribosomal RNA by the exosome complex and nucleolar RNAi inC. elegans

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