RNA memories: trans-generational epigenetic inheritance of RNA-mediated gene silencing
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PROVIDER: PRJNA521724 | ENA |
REPOSITORIES: ENA
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Project description:Trans-generational epigenetic inheritance (TEI), which functionally intersects RNA with histone modification, recently forced a reinterpretation of the interplay between gene expression and selective pressures. Our groups integrate genetic, genomic, dynamic imaging, biochemistry and proteomic technologies to provide a functional mechanistic understanding of the interplay of TEI and the RNA interference (RNAi) phenomena in the nematode C. elegans. We discovered a family of proteins (the nuclear Argonaute-interacting proteins or NIPs), which controls the strength, inheritance and gene target specificity of nuclear RNAi. Loss of NIP-1 and NIP-2 in the soma leads to an enhancement of nuclear RNAi activities without affecting cytoplasmic RNAi. Loss of NIP-3 in the germline disables TEI and leads to a profoundly impaired response to transposable genomic elements (viral-like sequences). The genome of nip-3 mutants becomes de-stabilized; spontaneous visible mutations arise at high frequency due to an unbridled mobilization of a subset of transposable elements. Surprisingly, silencing of a distinct subset of transposable elements is coincidentally enhanced. Finally, expression imaging revealed an eminent role for the maturing male germline in TEI. This data supports a model wherein NIPs determine the potency and stability of TEI by gating and sorting small RNAs (which provide specificity) towards germline and somatic nuclear RNAi and epigenetic machineries. Our work further implies that this molecular machinery evolved to atone an animal’s epigenetic memory to preserve a species’ integrity in face of genetic pathogens.
2020-03-09 | GSE126377 | GEO
Project description:Trans-Generational Hormesis and the Inheritance of Aging Resistance
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Project description:Animals respond to dietary changes by adapting their metabolism to available nutrients through insulin and insulin-like growth factor signalling. Restricting calorie intake generally extends life and health span, but Drosophila fed non-ideal sugars such as galactose are stressed and have shorter life spans. Here, we report that although these flies have shorter life spans, their offspring show significant life extension if switched to a normal sugar (glucose) diet. We define this as TGH or trans-generational hormesis, a beneficial effect that comes from a mild stress. We trace the effects to changes in stress responses in parents, ROS production, effects on lipid metabolism, and changes in chromatin and gene expression. We find that this mechanism is similar to what happens to the long lived Indy mutants on normal food, but surprisingly find that Indy is required for life span extension for galactose fed flies. Indy mutant flies grown on galactose do not live longer as do their siblings grown on glucose, rather overexpression of Indy rescues lifespan for galactose reared flies. We define a process where sugar metabolism can generate epigenetic changes that are inherited by offspring, providing a mechanism for how transgenerational nutrient sensitivities are passed on.
2017-07-01 | GSE97233 | GEO
Project description:Trans-generational inheritance of a phenotypically neutral epimutation enables descendants to reinstate an ancestral silencing episode
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Project description:Piwi interacting (pi)RNAs repress diverse transposable elements in the germ cells of metazoans and are essential for fertility in both invertebrates and vertebrates. The precursors of piRNAs are transcribed from distinct genomic regions, the so-called piRNA clusters; however, how piRNA clusters are differentiated from the rest of the genome is not known. To address this question, we studied piRNA biogenesis in two Drosophila virilis strains that show differential ability to generate piRNAs from several genomic regions. We found that active piRNA biogenesis correlates with high levels of histone 3 lysine 9 trimethylation (H3K9me3) over genomic regions that give rise to piRNAs. Furthermore, piRNA biogenesis in the progeny requires the trans-generational inheritance of an epigenetic signal, presumably in form of homologous piRNAs that are generated in the maternal germline and deposited into the oocyte. The inherited piRNAs enhance piRNA biogenesis by installment of H3K9me3 mark on piRNA clusters and by promoting ping-pong processing of homologous transcripts into mature piRNAs. We submitted the resequencing data together with the functional genomic datasets because it was generated with the sole purpose of supporting those. The SRA accession numbers are SRR1536176 and SRR1536175. ChIP-seq against H3K9me3 and Pol2, Total RNA-seq, in Drosophila virilis Strain9 and Strain160 as well as crosses between them
2014-09-01 | E-GEOD-59965 | biostudies-arrayexpress
Project description:Animals respond to dietary changes by adapting their metabolism to available nutrients through insulin and insulin-like growth factor signalling. Restricting calorie intake generally extends life and health span, but Drosophila fed non-ideal sugars such as galactose are stressed and have shorter life spans. Here, we report that although these flies have shorter life spans, their offspring show significant life extension if switched to a normal sugar (glucose) diet. We define this as TGH or trans-generational hormesis, a beneficial effect that comes from a mild stress. We trace the effects to changes in stress responses in parents, ROS production, effects on lipid metabolism, and changes in chromatin and gene expression. We find that this mechanism is similar to what happens to the long lived Indy mutants on normal food, but surprisingly find that Indy is required for life span extension for galactose fed flies. Indy mutant flies grown on galactose do not live longer as do their siblings grown on glucose, rather overexpression of Indy rescues lifespan for galactose reared flies. We define a process where sugar metabolism can generate epigenetic changes that are inherited by offspring, providing a mechanism for how transgenerational nutrient sensitivities are passed on.
2017-07-01 | GSE97162 | GEO
Project description:Cytosine DNA methylation regulates the expression of eukaryotic genes and transposable elements. Methylation is copied by DNA methyltransferases after DNA replication, which results in faithful transmission of methylation patterns during cell division and, at least in flowering plants, across generations. Trans-generational inheritance is mediated by a small group of cells that includes gametes and their progenitors. However, methylation is usually analyzed in somatic tissues that do not contribute to the next generation, and the mechanisms of trans-generational inheritance are inferred from such studies. To gain a better understanding of how DNA methylation is inherited, we analyzed purified Arabidopsis thaliana sperm and vegetative cells – the cell types that comprise pollen – with mutations in the DRM, CMT2 and CMT3 methyltransferases.
2016-12-13 | GSE87170 | GEO
Project description:Piwi interacting (pi)RNAs repress diverse transposable elements in the germ cells of metazoans and are essential for fertility in both invertebrates and vertebrates. The precursors of piRNAs are transcribed from distinct genomic regions, the so-called piRNA clusters; however, how piRNA clusters are differentiated from the rest of the genome is not known. To address this question, we studied piRNA biogenesis in two Drosophila virilis strains that show differential ability to generate piRNAs from several genomic regions. We found that active piRNA biogenesis correlates with high levels of histone 3 lysine 9 trimethylation (H3K9me3) over genomic regions that give rise to piRNAs. Furthermore, piRNA biogenesis in the progeny requires the trans-generational inheritance of an epigenetic signal, presumably in form of homologous piRNAs that are generated in the maternal germline and deposited into the oocyte. The inherited piRNAs enhance piRNA biogenesis by installment of H3K9me3 mark on piRNA clusters and by promoting ping-pong processing of homologous transcripts into mature piRNAs. We submitted the resequencing data together with the functional genomic datasets because it was generated with the sole purpose of supporting those. The SRA accession numbers are SRR1536176 and SRR1536175.
2014-09-01 | GSE59965 | GEO
Project description:DNA methylation is a chromatin modification that contributes to epigenetic regulation of gene expression. The inheritance patterns and trans-generational stability of 962 differentially methylated regions (DMRs) were assessed in a panel of 71 near-isogenic lines (NILs) derived from maize (Zea mays) inbred lines B73 and Mo17. The majority of DMRs exhibit inheritance patterns that would be expected for local (cis) inheritance of DNA methylation variation such that DNA methylation level was coupled to local genotype. There are few examples of DNA methylation that exhibit trans-acting control or paramutation-like patterns. The cis-controlled DMRs provided an opportunity to study the stability of inheritance for DNA methylation variation. There was very little evidence for alterations of DNA methylation levels at the cis-controlled DMRs during NIL population development. DNA methylation level was associated with local genotypes in all of the >30,000 examined cases except one. Additionally, the majority of the DMRs were not associated with small RNA. Together, our results suggest that a significant portion of DNA methylation variation in maize exhibits cis-controlled inheritance patterns, is highly stable and does not require active programming by small RNAs for maintenance. Methylation profiles in seedling tissue of maize near-isogenic lines (NILs) derived from B73 and Mo17 using a custom 12x270K NimbleGen array.
2014-04-01 | E-GEOD-51567 | biostudies-arrayexpress
Project description:Gene expression evolution can be caused by changes in cis- or trans-regulatory elements or both. As cis and trans regulation operate through different molecular mechanisms, cis and trans mutations may show different inheritance patterns and may be subjected to different selective constraints. To investigate these issues, we obtained and analyzed gene expression data from two Saccharomyces cerevisiae strains and their hybrid, using high-throughput sequencing. Our data indicate that compared to other types of genes, those with antagonistic cis-trans interactions are more likely to exhibit over- or under-dominant inheritance of expression level. Moreover, in accordance with previous studies, genes with trans variants tend to have a dominant inheritance pattern while cis variants are enriched for additive inheritance. In addition, cis regulatory differences contribute more to expression differences between species than within species, whereas trans regulatory differences show a stronger association between divergence and polymorphism. Our data indicate that in the trans component of gene expression differences genes subjected to weaker selective constraints tend to have an excess of polymorphism over divergence compared to those subjected to stronger selective constraints. In contrast, in the cis component, this difference between genes under stronger and weaker selective constraint is mostly absent. To explain these observations, we propose that purifying selection more strongly shapes trans polymorphism than cis polymorphism. Study the gene expression patterns in two strains of yeast (BY and RM)
2013-11-10 | E-GEOD-46838 | biostudies-arrayexpress