Synthetic circuit identifies subpopulations with sustained memory of DNA damage
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ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE36210 | GEO | 2012/03/02
SECONDARY ACCESSION(S): PRJNA152887
REPOSITORIES: GEO
Similar Datasets
Project description:Differential responses to stimuli can affect how cells succumb to disease. In yeast, DNA damage can create heterogeneous responses. To delineate how a response contributes to a cell's future behavior, we constructed a transcription-based memory circuit that detects DNA repair to isolate subpopulations with heritable damage responses. Strongly responsive cells show multigenerational effects, including growth defects and iron-associated gene expression. Less-responsive cells exhibit increased mutation frequencies but resume wild-type behavior. These two subpopulations remain distinct for multiple generations, indicating a transmissible memory of damage. Collectively, this work demonstrates the efficacy of using synthetic biology to define how environmental exposure contributes to distinct cell fates. Cells containing the HUG1 memory device (Burrill, 2011) were exposed to 0.3% EMS for 24 h and recovered for 36 h, at which point cells were sorted based on YFP expression, i.e. memory and non-memory cells. These two sorted populations were then grown for another 12 h, at which point transcriptional profiling was performed.
2012-03-02 | E-GEOD-36210 | biostudies-arrayexpress
Project description:Cells respond heterogeneously to DNA damage. We engineered genetic circuits to detect differential responses in a population that persist for many days post-stimulus. We used microarrays to compare memory and non-memory subpopulations 3 days after DNA damage or doxycycline exposure. MD12/p53R2-RE and MD10/TetOx2 cells were either exposed to UV (10uJ/m^2) or doxycycline (1 ug/mL, 24 hours) and allowed to recover 3 days before sortng of memory and non-memory cells and RNA extraction. Two replicates were submitted for each condition (UV memory, UV non-memory, dox memory, dox non-memory)
2012-05-23 | E-GEOD-38189 | biostudies-arrayexpress
Project description:Cells respond heterogeneously to DNA damage. We engineered genetic circuits to detect differential responses in a population that persist for many days post-stimulus. We used microarrays to compare memory and non-memory subpopulations 3 days after DNA damage or doxycycline exposure.
2012-05-24 | GSE38189 | GEO
Project description:Synthetic circuit identifies subpopulations with sustained memory of DNA damage
| PRJNA152887 | ENA
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:Arabidopsis thaliana plants that have experienced an initial exposure to dehydration stress (“trained plants”) have an increased ability to maintain leaf relative water content (RWC) during subsequent stresses than plants experiencing the stress for the first time and transcription of selected dehydration response genes is altered during successive exposures to dehydration stress. This physiological and transcriptional behavior of trained plants is consistent with a “memory “of an earlier stress. It is unknown whether such memory is present in other Angiosperm lineages and whether it is an evolutionarily conserved response to stress (see E-GEOD-48235). Here, we analyzed the behavior and transcriptomes of maize (Zea mays) plants experiencing multiple dehydration stresses and compare them with responses of the evolutionarily distant A. thaliana. We found structurally related genes in maize that displayed the same memory-type responses as in A. thaliana, providing evidence of the conservation of function and transcriptional memory in the evolution of plants’ dehydration stress response systems. Similar to A. thaliana, trained Z. mays plants retained higher RWC during dehydration stress than untrained plants, due in part to maintaining reduced stomatal conductance, despite full recovery of RWC, after the first stress. Divergent transcriptional memory responses were also expressed, suggesting diversification of function among stress memory genes. Some dehydration stress memory genes were also shared with other stress and hormone responding pathways, indicating complex and dynamic interactions between different plant signaling networks. The results provide new insight into how plants respond to multiple dehydration stresses and provide a platform for studies of the functions of memory genes in adaptive responses to water deficit in monocot and eudicot plants . For each condition (water, S1, and S3) the transcriptome was sequenced for two replicates. The watered condition is considered the control.
2014-08-01 | E-GEOD-48507 | biostudies-arrayexpress
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
Project description:Inflammatory Memory in Epidermal Stem Cells Accelerates Tissue Damage Responses
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Project description:Arabidopsis plants that have experienced stress from water withdrawal show an improved ability to tolerate subsequent exposures as a ‘memory’ from the previous stress. This physiological stress memory is associated with ‘transcriptional memory’ illustrated by a subset of dehydrations stress responding genes that produce significantly different transcript amounts during repeated dehydration stresses relative to their response in the first. Here we report the genome-wide representation of dehydration stress transcriptional memory genes in A. thaliana. We identify four novel transcription patterns in response to repeated dehydration stress treatments. The nature of the proteins encoded by genes from each type of memory-response pattern is analyzed and the consequences of the genes’ memory behavior are considered in the context of possible biological relevance. The memory behavior of genes co-regulated by the dehydration/ABA and other abiotic stress and hormone responding pathways suggested that the crosstalk at the transcriptional level between them was affected as well. The intensity and the nature of specific biochemical, membrane, chloroplast, and stress response-related interactions during multiple exposures to dehydration stress are different from the responses to a single dehydration stress. The results reveal additional, hitherto unknown, levels of complexity of the plants’ transcriptional behavior when adjusting and adapting to recurring water deficits. For each condition (water, S1, and S3) the transcriptome was sequenced for two replicates. The watered condition is considered the control.
2014-01-01 | E-GEOD-48235 | biostudies-arrayexpress
Project description:Enhanced secondary Ab responses are a vital component of adaptive immunity, yet little is understood about the intrinsic and extrinsic regulators of naïve and memory B cells that results in differences in their responses to Ag. Microarray analysis, together with surface and intracellular phenotyping, revealed that memory B cells have increased expression of members of the TNF receptor, SLAM, B7 and Bcl2 families, as well as the TLR-related molecule CD180 (RP105). Accordingly, memory B cells exhibited enhanced survival, proliferation and Ig secretion, as well as entered division more rapidly than naïve B cells in response to both T-dependent and T-independent stimuli. Furthermore, both IgM and isotype switched memory B cells, but not naïve B cells, co-stimulated CD4+ T cells in vitro through a mechanism dependent on their constitutive expression of CD80 and CD86. This study demonstrates that upregulation of genes involved in activation, co-stimulation and survival provides memory B cells with a unique ability to produce enhanced immune responses and contributes to the maintenance of the memory B cell pool. Keywords: cell type comparison Four subsets of human splenic B cells (naïve, IgM-memory, Ig isotype switched memory and plasma cells); sort-purified and analysed immediately ex vivo; performed in duplicate.
2008-12-30 | E-GEOD-13411 | biostudies-arrayexpress