Multigenerational Proteolytic Inactivation of Restriction Upon Subtle Genomic Hypomethylation in Pseudomonas aeruginosa
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PROVIDER: PRJNA1285262 | ENA |
REPOSITORIES: ENA
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Project description:Multigenerational Proteolytic Inactivation of Restriction Upon Subtle Genomic Hypomethylation
| PRJNA1179457 | ENA
Project description:In Pseudomonas aeruginosa, restriction inactivation upon growth at high temperatures was previously described, however, which system is being inactivated, the underlying mechanism, as well as the timing of recovery, remain unknown. Here, we report that P. aeruginosa Type I methyltransferase (HsdMS) and restriction endonuclease (HsdR) components are degraded by two Lon-like proteases when replicating above 41 °C, which induces partial genome hypomethylation and simultaneously prevents self-targeting, respectively. Interestingly, upon return to 37 °C, methyltransferase activity returns gradually, with restriction activity not fully recovering for over 60 bacterial generations, representing the longest bacterial memory to our knowledge. Forced expression of HsdR over the first 45 generations is toxic, demonstrating the fitness benefit of HsdR inactivation.
2025-06-03 | GSE280585 | GEO
Project description:Restriction-modification (R-M) systems protect against phage infection by detecting and degrading invading foreign DNA. However, like many prokaryotic anti-phage defenses, R-M systems pose a significant risk of auto-immunity, exacerbated by the presence of hundreds to thousands of potential cleavage sites in the bacterial genome. Pseudomonas aeruginosa strains experience the temporary inactivation of restriction endonucleases (tiREN) upon growth at high temperatures, but the mechanisms and implications of this are unknown. Here, we report that P. aeruginosa Type I restriction endonuclease (HsdR) is degraded, and the methyltransferase (HsdMS) is partially degraded, by two Lon-like proteases when replicating above 41 °C. This post-translational regulation prevents self-DNA targeting and leads to partial genomic hypomethylation, as demonstrated by SMRT sequencing and eTAM-seq. Interestingly, upon return to 37 ºC, restriction activity and full genomic methylation do not fully recover for up to 60 bacterial generations. Our findings demonstrate that Type I R-M is tightly regulated post-translationally with a long memory effect that ensures genomic stability and mitigates auto-toxicity.
2025-07-09 | GSE301453 | GEO
Project description:TCDD exposure cauuses multigenerational effect in mice.
2023-01-18 | GSE220204 | GEO
Project description:The notion that genes are the sole units of heredity and that a barrier exists between soma and germline has been a major hurdle in elucidating the heritability of traits that were observed to follow a non-Mendelian inheritance pattern. It was only after the conception of “epigenetics” by C. H. Waddington that the effect of parental environment on subsequent generations via non-DNA sequence-based mechanisms, such as DNA methylation, chromatin modifications, non-coding RNAs and proteins, could be established in various organisms, now referred to as multigenerational epigenetic inheritance. Despite the growing body of evidence, the male gamete-derived epigenetic factors that mediate the transmission of such phenotypes are seldom explored, particularly in the model organism Drosophila melanogaster. Using the heat stress-induced multigenerational epigenetic inheritance paradigm in a widely used position-effect variegation line of Drosophila, named white-mottled, we have dissected the effect of heat stress on the sperm proteome in the current study. We demonstrate that multiple successive generations of heat stress at the early embryonic stage results in a significant downregulation of proteins associated with translation, chromatin organization, microtubule-based processes, and generation of metabolites and energy in the Drosophila sperms. Based on our findings, we propose chromatin-based epigenetic mechanisms, a well-established mechanism for environmentally induced multigenerational effects, as a plausible way of transmitting heat stress memory via the male germ line in subsequent generations. Moreover, we demonstrate the effect of multiple generations of heat stress on the reproductive fitness of Drosophila, shedding light on the adaptive or maladaptive potential of heat stress-induced multigenerational phenotypes.
2024-05-10 | PXD037488 | Pride
Project description:Wild-type P53 proteolytic inactivation by asparagine endopeptidase promotes glioblastoma progression
| PRJNA414419 | ENA
Project description:TCDD-mediated multigenerational effects in mice
| PRJNA909233 | ENA
Project description:Transgenerational effects likely have wide-ranging implications for human health, biological adaptation and evolution, however their mechanism and biology remain poorly understood. Here we demonstrate that a germline nuclear small RNA/chromatin pathway can maintain epi-allelic inheritance for many generations when triggered by a piRNA-dependent foreign RNA response in C. elegans. Using forward genetic screens and candidate approaches we find that a core set of nuclear RNAi and chromatin factors are required for multigenerational inheritance of environmental RNAi and piRNA silencing. These include a germline-specific nuclear Argonaute HRDE1/WAGO-9, a HP1 otholog HPL-2 and two putative histone methyltransferases, SET-25 and SET-32. Most surprisingly, piRNAs can trigger highly stable long-term silencing lasting at least 20 generations. Once established, this long-term memory becomes independent of the piRNA trigger but remains dependent on the nuclear RNAi/chromatin pathway. Our data present the first report of multigenerational epigenetic inheritance induced by piRNAs in any organism. Seven C. elegans small RNA libraries from three distinct experiments (A, B, C) were sequenced using Illumina sequencing technology. Five small RNA libraries were prepared according to library construction protocol 1 and sequenced as part of 22 flow cell lanes on the Illumina GA IIx platform. Samples were labelled for multiplexing using 4-bp 5'-barcodes, a single flow cell lane included several multiplexed libraries. Two small RNA libraries were prepared according to library construction protocol 2 and sequenced on the Illumina MiSeq platform.
2012-06-25 | E-GEOD-38813 | biostudies-arrayexpress
Project description:We examined the impact of paternal abstinence following morphine self_administration on the transmission of multigenerational factors from the F0 to the F1 generation. Previously, we found that offspring of non_abstinent, morphine administering male rats showed increased morphine_taking, diminished adolescent social play, and reduced sensitivity to morphine analgesia. Here, we show that these phenotypes are normalized in the offspring of fathers who were 90 days abstinent from morphine at the time of breeding. We further compared the small RNA content of sperm collected from non_abstinent versus 90 days abstinent F0 males to identify candidate molecules correlated with transmission of morphine_induced multigenerational phenotypes.
2025-05-30 | GSE274906 | GEO
Project description:Given the risk of environmental pollution by pharmaceutical compounds and the effects of these compounds on exposed ecosystems, ecologically relevant and realistic assessments are required. However, many studies have been mostly focused on individual responses in a single generation exposed to one-effect concentration. Here, transcriptional responses of the crustacean Daphnia magna to the antibiotic tetracycline across multiple generations and effect concentrations were investigated. The results demonstrated that tetracycline induced different transcriptional responses of daphnids that were dependent on dose and generation. For example, reproduction-related expressed sequence tags (ESTs), including vitellogenin, were distinctly related to the dose-dependent tetracycline exposure, whereas multigenerational exposure induced significant change of molting-related ESTs such as cuticle protein. Sixty-five ESTs were shared in all contrasts, suggesting a conserved mechanism of tetracycline toxicity regardless of exposure concentration or time. Most of them were associated with general stress responses including translation, protein and carbohydrate metabolism, and oxidative phosphorylation. In addition, effects across the dose-response curve showed higher correlative connections among transcriptional, physiological, and individual responses than multigenerational effects. In the multigenerational exposure, the connectivity between adjacent generations decreased with increasing generation number. The results clearly highlight that exposure concentration and time trigger different mechanisms and functions, providing further evidence that multigenerational and dose-response effects cannot be neglected in environmental risk assessment.
2017-10-16 | GSE94439 | GEO