Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Three Rules Explain Transgenerational Small RNA Inheritance in C. elegans

ABSTRACT: Life experiences trigger transgenerational small RNA-based responses in C. elegans nematodes1. Dedicated machinery ensures that heritable effects would re-set, typically after a few generations2,3. Here we show that isogenic individuals differ dramatically in the persistence of transgenerational responses. By examining lineages composed of >20,000 worms we reveal 3 inheritance rules: (1) Once a response is initiated, each isogenic mother stochastically assumes an “inheritance state”, establishing a commitment that determines the fate of the inheritance. (2) The response that each mother transfers is uniform in each generation of her descendants. (3) The likelihood that an RNAi response would transmit to the progeny increases the more generations the response lasts, according to a “hot hand” principle. Mechanistically, the different parental “inheritance states” correspond to global changes in the expression levels of endogenous small RNAs, immune response genes, and targets of the conserved transcription factor HSF-1. We show that these rules predict the descendants’ developmental rate and resistance to stress.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE149422 | GEO | 2020/08/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Three Rules Explain Transgenerational Small RNA Inheritance in C. elegans

Project description:Three Rules Explain Transgenerational Small RNA Inheritance in C. elegans

| PRJNA628654 | ENA

The chromatin modifiers SET-25 and SET-32 are required for initiation but not long-term maintenance of transgenerational epigenetic inheritance

Project description:Some epigenetic modifications are inherited from one generation to the next, providing a potential mechanism for the inheritance of environmentally acquired traits. Transgenerational inheritance of RNA interference phenotypes in C. elegans provides an excellent model to study this phenomenon, and whilst studies have implicated both chromatin modifications and small RNA pathways in heritable silencing their relative contributions remain unclear. Here we demonstrate that the histone methyltransferases SET-25 and SET-32 are required for the establishment of a transgenerational silencing signal, but not for long-term maintenance of this signal between subsequent generations suggesting that transgenerational epigenetic inheritance is a multi-step process, with distinct genetic requirements for establishment and maintenance of heritable silencing. Furthermore, small RNA sequencing reveals that the abundance of secondary siRNA (thought to be the effector molecules of heritable silencing) does not correlate with silencing phenotypes. Together, our results suggest that the current mechanistic models of epigenetic inheritance are incomplete.

2018-10-30 | PXD008754 | Pride

Germ Granules Govern Small RNA Inheritance

Project description:In C. elegans nematodes, components of liquid-like germ granules were shown to be required for transgenerational small RNA inheritance. Surprisingly, we show here that mutants with defective germ granules can nevertheless inherit potent small RNA-based silencing responses, but some of the mutants lose this ability after many generations of homozygosity. Animals mutated in pptr-1, which is required for stabilization of P granules in the early embryo, display extraordinarily strong heritable RNAi responses, lasting for tens of generations. Intriguingly, the RNAi capacity of descendants derived from mutants defective in the core germ granules proteins MEG-3 and MEG-4 is determined by the genotype of the ancestors, and changes transgenerationally. Further, whether the meg-3/4 mutant alleles were present in the paternal or maternal lineages lead to different transgenerational consequences. Small RNA inheritance, rather than maternal contribution of the germ granules themselves, mediates the transgenerational defects in RNAi of meg-3/4 mutants and their progeny. Accordingly, germ granule defects lead to heritable genome-wide mis-expression of endogenous small RNAs. Upon disruption of germ granules, hrde-1 mutants can inherit RNAi although HRDE-1 was previously thought to be absolutely required for RNAi inheritance. We propose that germ granules sort and shape the RNA pool, and that small RNA inheritance maintains this activity for multiple generations.

2019-07-31 | GSE128112 | GEO

Hierarchical rules for Argonaute loading in Drosophila

Project description:Drosophila Argonaute-1 and Argonaute-2 differ in function and small RNA content. AGO2 binds to siRNAs, whereas AGO1 is almost exclusively occupied by microRNAs. microRNA duplexes are intrinsically asymmetric, with one strand, the miR strand, preferentially entering AGO1 to recognize and regulate the expression of target mRNAs. The other strand, miR*, has been viewed as a by-product of microRNA biogenesis. Here, we show that miR*s are often loaded as functional species into AGO2. This indicates that each microRNA precursor can potentially produce two mature small RNA strands that are differentially sorted within the RNAi pathway. miR* biogenesis depends upon the canonical microRNA pathway, but loading into AGO2 is mediated by factors traditionally dedicated to siRNAs. By inferring and validating hierarchical rules that predict differential AGO loading, we find that intrinsic determinants, including structural and thermodynamic properties of the processed duplex, regulate the fate of each RNA strand within the RNAi pathway.

2009-11-15 | GSE17734 | GEO

H3K9me2 protects lifespan against the transgenerational burden of germline transcription in C. elegans

Project description:Chromatin state influences lifespan and may allow for the epigenetic inheritance of this complex trait. At sites of active transcription, the COMPASS complex methylates histone H3 at lysine 4 (H3K4me). In Caenorhabditis elegans, reductions in COMPASS extend lifespan, and wild-type descendants of COMPASS mutants inherit longevity for four generations. Here we show that the longevity of COMPASS mutants is itself a transgenerational trait caused by gradual changes in the repressive chromatin factor H3K9me2. H3K9me2 is required for longevity in COMPASS mutants and can confer longevity when increased in other chromatin modifier mutants. H3K9me2 levels also correlate with a transgenerational decline in wild-type lifespan after freezing or starvation. We propose that germline transcription-coupled H3K4me encroaches on H3K9me2 to limit lifespan. Loss of COMPASS complex alleviates the burden of H3K4me and therefore extends lifespan. This study suggests a causal role for a single heterochromatin factor in the establishment and inheritance of longevity.

2019-12-17 | GSE129928 | GEO

Molecular rules governing de novo methylation in cancer

Project description:De novo methylation of CpG islands is seen in many tumors, but the general rules governing this process are not known. By analyzing DNA from tumors, as well as normal tissues, and by utilizing a wide range of published data, we have been able to identify a well-defined set of tumor targets, each of which has its own “coefficient” of methylation that is largely determined by its inherent relative ability to recruit the polycomb complex. This pattern is initially formed by a slow process of de novo methylation that occurs during aging and then undergoes expansion early in tumorigenesis, where it may play a role as an inhibitor of development-associated gene activation. We also demonstrate that DNA methylation patterns can be used to diagnose the primary tissue source of tumor metastases.

2014-03-26 | GSE38142 | GEO

Hierarchical rules for Argonaute loading in Drosophila

2009-11-15 | E-GEOD-17734 | biostudies-arrayexpress

Molecular rules governing de novo methylation in cancer

Project description:De novo methylation of CpG islands is seen in many tumors, but the general rules governing this process are not known. By analyzing DNA from tumors, as well as normal tissues, and by utilizing a wide range of published data, we have been able to identify a well-defined set of tumor targets, each of which has its own M-bM-^@M-^\coefficientM-bM-^@M-^] of methylation that is largely determined by its inherent relative ability to recruit the polycomb complex. This pattern is initially formed by a slow process of de novo methylation that occurs during aging and then undergoes expansion early in tumorigenesis, where it may play a role as an inhibitor of development-associated gene activation. We also demonstrate that DNA methylation patterns can be used to diagnose the primary tissue source of tumor metastases. CpG-methylated genomic DNA was enriched using a methyl-DNA immunoprecipitation (mDIP) assay. DNA from the input and bound (enriched) DNA for each sample were labeled and hybridized on the array to define the methylation state of each region.

2014-03-26 | E-GEOD-38142 | biostudies-arrayexpress

Epigenetic Transgenerational Alterations to Stress Response in Brain Gene Networks and Behaviour

Project description:Ancestral environmental exposures that promote epigenetic transgenerational inheritance influence all aspects of an individual’s life history. Stress experienced during adolescence can affect adult physiological and behavioural phenotypes. The current study utilized a systems biology approach to investigate the interactions of these two forms of epigenetic modification, one carried in the germline transgenerationally and the other contained in the context of life history. A transgenerational epigenetic imprint left by the fungicide vinclozolin promoted regional specific brain gene networks that influenced chronic restraint stress responses to alter adult physiological, brain and behavioural phenotypes. The environmentally-induced epigenetic transgenerational inheritance was found to interact with early life stress response to impact the adult brain genome activity to bring “the phenotype into being”. We used microarrays to determine genes expressed differentially in rats' 4 brain areas - basolateral amygdala (BLA), primary and secondary motor cortex (Crtx), CA1 of the hippocampus (CA1), and CA3 of the hippocampus (CA3) - due to Vinclozolin treatments of their grand-grandmothers and/or to stress in adolescence age. For each of 4 brain areas (BLA, CRTX, CA1, and CA3), RNA samples from 4 treatment groups - stressed control (St-Con), non-stressed control (NSt-Con), stressed vinclozolin (St-Vin), and non-stressed vinclozolin (NSt-Vin) - were compared to each other. Each treatment groups contained 3 biological replica. RNA for each replica was pooled from 4 individual animals forming a certain dyad group.

2012-02-01 | E-GEOD-26737 | biostudies-arrayexpress

Developmental Origins of Transgenerational Sperm DNA Methylation Epimutations Following Ancestral DDT Exposure

Project description:In previous studies, the pesticide DDT was shown to promote the transgenerational inheritance of sperm differential DNA methylation regions (DMRs), also called epimutations, which can mediate this epigenetic inheritance. In the current study, the developmental origins of the transgenerational DMRs during gametogenesis have been investigated. Male control and DDT lineage F3 generation rats were used to isolate embryonic day 16 (E16) prospermatogonia, postnatal day 10 (P10) spermatogonia, adult pachytene spermatocytes, round spermatids, caput epididymal spermatozoa, and caudal sperm. The DMRs between the control versus DDT lineage samples were determined at each developmental stage. The top 100 statistically significant DMRs at each stage were compared and the developmental origins of the caudal epididymal sperm DMRs were assessed.

2019-01-19 | GSE121585 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data