Small RNAs Worm Up Transgenerational Epigenetics Research

Grishok, Alla

doi:10.3390/dna1020005

Cited by 10 publications

(9 citation statements)

References 92 publications

(143 reference statements)

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“…Epigenetic inheritance of gene expression states operates in C. elegans through small RNAs and histone modifications (Frolows & Ashe, 2021; Grishok, 2021; Ketting & Cochella, 2021; Phillips & Updike, 2022; Quarato et al , 2022; Seroussi et al , 2022). Briefly, small RNAs bound to specific Argonaute proteins enter the nucleus and induce histone modifications such as repressive H3K9me3 or H3K27 methylation at the corresponding locus, thereby silencing gene expression (Gu et al , 2012; Mao et al , 2015).…”

Section: Introductionmentioning

confidence: 99%

Genome‐wide association and environmental suppression of the mortal germline phenotype of wild C. elegans

Frézal,

Saglio,

Zhang

et al. 2023

EMBO Reports

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The animal germline lineage needs to be maintained along generations. However, some Caenorhabditis elegans wild isolates display a mortal germline phenotype, leading to sterility after several generations at 25°C. Using a genome‐wide association approach, we detect a significant peak on chromosome III around 5 Mb, confirmed by introgressions. Thus, a seemingly deleterious genotype is maintained at intermediate frequency in the species. Environmental rescue is a likely explanation, and indeed associated bacteria and microsporidia suppress the phenotype of wild isolates as well as mutants in small RNA inheritance (nrde‐2) and histone modifications (set‐2). Escherichia coli strains of the K‐12 lineage suppress the phenotype compared to B strains. By shifting a wild strain from E. coli K‐12 to E. coli B, we find that memory of the suppressing condition is maintained over several generations. Thus, the mortal germline phenotype of wild C. elegans is in part revealed by laboratory conditions and may represent variation in epigenetic inheritance and environmental interactions. This study also points to the importance of non‐genetic memory in the face of environmental variation.

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Section: Introductionmentioning

confidence: 99%

Genome‐wide association and environmental suppression of the mortal germline phenotype of wild C. elegans

Frézal,

Saglio,

Zhang

et al. 2023

EMBO Reports

View full text Add to dashboard Cite

show abstract

“…Epigenetic inheritance of gene expression states operates in C. elegans through small RNAs and histone modifications (Ketting and Cochella 2021;Frolows and Ashe 2021;Grishok 2021;Seroussi et al 2022;Phillips and Updike 2022;Quarato et al 2022). Briefly, small RNAs bound to specific Argonaute proteins enter the nucleus and induce histone modifications such as repressive H3K9me3 or H3K27 methylation at the corresponding locus, thereby silencing gene expression (Gu et al 2012;Mao et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide association and environmental suppression of the mortal germline phenotype of wildC. elegans

Frézal,

Saglio,

Zhang

et al. 2023

Preprint

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The animal germline lineage needs to be maintained along generations. However, some Caenorhabditis elegans wild isolates display a mortal germline phenotype, whereby the lineage becomes sterile after several generations at 25C. We used a genome-wide association approach to study the genetic basis for this phenotype in C. elegans populations. We detected a significant peak on chromosome III around 5 Mb, which was confirmed using introgression lines. These results indicate that a seemingly deleterious genotype is maintained at intermediate frequency in the species. Environmental rescue is a likely explanation and we indeed find that naturally associated bacteria and microsporidia suppressed the phenotype. The tested bacteria also suppressed the temperature-sensitive mortal germline phenotype of mutants in small RNA inheritance (nrde-2) and histone modifications (set-2). Even Escherichia coli strains of the K-12 lineage suppressed the phenotype compared to B strains. By shifting a strain cultured on E. coli K-12 back to E. coli B, we found that C. elegans can keep over several generations the memory of the suppressing conditions. Thus, the mortal germline phenotype of wild C. elegans is in part revealed by laboratory conditions and may represent variation in epigenetic inheritance and environmental interactions. This study also points to the importance of non-genetic memory in the face of environmental variation.

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“…In fact, lifestyle interventions are known as potent drivers of neural plasticity in all type of organisms (Mora, 2013)(Valero et al, 2016)(Phillips, 2017)(Maharjan et al, 2020). Besides, the heritability of these lifestyle effects to either the next generation (intergenerational inheritance) or the second and later generations (transgenerational inheritance (Jirtle & Skinner, 2007)) has been largely explored in different taxa (Baugh & Day, 2020)(Frolows & Ashe, 2021)(Grishok, 2021)(Chey & Jose, 2022)(Zare et al, 2018)(Deas et al, 2019)(Hoyer-Fender, 2020)(Mu et al, 2021). It has also been explored in different models, with a special focus in stress or diet (Blaze & Roth, 2015)(Hime et al, 2021)(Lagisz et al, 2014)(Risal et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Transgenerational effects of exercise on mouse brain and cognition

Cintado

Tezanos

Casas

et al. 2023

Preprint

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Lifestyle induces long lasting effects on brain and cognition, with some interventions like stress including transgenerational inheritance mediated by epigenetic mechanisms. Physical exercise is one lifestyle intervention driving robust improvements of cognition, including intergenerational transmission to the litter. However, little is known about whether exercise effects are transgenerationally transmitted. Here we analyzed adult hippocampal neurogenesis (AHN) and behavioral phenotype of sedentary adult male mice of F2 generation of exercised grandfathers (F0). Both F1 and F2 were sedentary, while F0 performed moderate exercise. We found F2 mice from exercised F0 acquired and recalled both spatial and non-spatial information better than F2 from sedentary F0. Contextual fear conditioning was not affected, together with no differences in AHN markers. Hippocampal smallRNAseq analysis revealed 35 significant differentially expressed (sDE) microRNAs (miRNAs) associated to relevant brain function families. Moreover, 11 of the 35 miRNAs target gene sets were found also enriched in F0 and F1, as well as target genes of 6 of them were differentially expressed also in F0 or F1. One of these 6 is miRNA-144, that together with miRNA-298 were found inversely correlated to cognitive index in F2. These results demonstrate that transgenerational transmission of the effects of exercise on specific cognitive tasks persists after two generations, even though some cellular changes induced in F1 vanish in F2. Thus, they suggest moderate exercise training has longer-lasting effects than previously thought, probably mediated by a small group of miRNAs acting across generations, and this is worth taking into account in public health programs.

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Small RNAs Worm Up Transgenerational Epigenetics Research

Cited by 10 publications

References 92 publications

Genome‐wide association and environmental suppression of the mortal germline phenotype of wild C. elegans

Genome‐wide association and environmental suppression of the mortal germline phenotype of wild C. elegans

Genome-wide association and environmental suppression of the mortal germline phenotype of wildC. elegans

Transgenerational effects of exercise on mouse brain and cognition

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