scholarly journals Transgenerational transcriptional heterogeneity from cytoplasmic chromatin

2022 ◽  
Author(s):  
Stamatis Papathanasiou ◽  
Nikos A. Mynhier ◽  
Shiwei Liu ◽  
Etai Jacob ◽  
Ema Stokasimov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Repression ◽  
Nuclear Architecture ◽  
Tumor Evolution ◽  
Histone 3 ◽  
Epigenetic State ◽  
Before And After ◽  
Transcriptional Changes ◽  
Cell Variation

Transcriptional heterogeneity from plasticity of the epigenetic state of chromatin is thought to contribute to tumor evolution, metastasis, and drug resistance. However, the mechanisms leading to nongenetic cell-to-cell variation in gene expression remain poorly understood. Here we demonstrate that heritable transcriptional changes can result from the formation of micronuclei, aberrations of the nucleus that are common in cancer. Micronuclei have fragile nuclear envelopes (NE) that are prone to spontaneous rupture, which exposes chromosomes to the cytoplasm and disrupts many nuclear activities. Using a combination of long-term live-cell imaging and same-cell, single-cell RNA sequencing (Look-Seq2), we identified significant reduction of gene expression in micronuclei, both before and after NE rupture. Furthermore, chromosomes in micronuclei fail to normally recover histone 3 lysine 27 acetylation, a critical step for the reestablishment of normal transcription after mitosis. These transcription and chromatin defects can persist into the next generation in a subset of cells, even after these chromosomes are incorporated into normal daughter nuclei. Moreover, persistent transcriptional repression is strongly associated with, and may be explained by, surprisingly long-lived DNA damage to these reincorporated chromosomes. Therefore, heritable alterations in transcription can originate from aberrations of nuclear architecture.

scholarly journals Transcriptional Changes Before and After Forgetting of a Long-Term Sensitization Memory in Aplysia californica

2018 ◽  
Author(s):  
Robert Calin-Jageman ◽  
Irina Calin-Jageman
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Memory Trace ◽  
Aplysia Californica ◽  
Regulation Of Expression ◽  
Withdrawal Reflex ◽  
Before And After ◽  
Transcriptional Changes ◽  
Testable Model

This is a pre-print of a paper now published in Neurobiology of Learning and Memory: https://doi.org/10.1016/j.nlm.2018.09.007 Most long-term memories are forgotten, becoming progressively less likely to be recalled. Still, some memory fragments may persist beyond forgetting, as savings memory (easier relearning) can persist long after recall has become impossible. What happens to a memory trace during forgetting that makes it inaccessible for recall and yet still effective to spark easier re-learning? We are addressing this question by tracking the transcriptional changes that accompany learning and then forgetting of a long-term sensitization memory in the tail-elicited siphon withdrawal reflex of Aplysia californica. First, we tracked savings memory. We found that even though recall of sensitization fades completely within 1 week of training, savings memory is still robustly expressed at 2 weeks post training. Next, we tracked the time-course of regulation of 11 transcripts we previously identified as potentially being regulated beyond the decay of recall. Remarkably, 3 transcripts still show strong regulation of expression 2 weeks after training and an additional 4 are regulated for at least 1 week. These long-lasting changes in gene expression always began early in the memory process, within 1 day of training. We present a synthesis of our results tracking gene expression changes accompanying sensitization and provide a testable model of how sensitization memory is forgotten.

scholarly journals Coordinated multitissue transcriptional and plasma metabonomic profiles following acute caloric restriction in mice

2006 ◽  
Vol 27 (3) ◽  
pp. 187-200 ◽  
Author(s):  
Colin Selman ◽  
Nicola D. Kerrison ◽  
Anisha Cooray ◽  
Matthew D. W. Piper ◽  
Steven J. Lingard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Caloric Restriction ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Proton Nuclear Magnetic Resonance ◽  
Cellular Transport ◽  
Expression Of Genes ◽  
Transcriptional Changes

Caloric restriction (CR) increases healthy life span in a range of organisms. The underlying mechanisms are not understood but appear to include changes in gene expression, protein function, and metabolism. Recent studies demonstrate that acute CR alters mortality rates within days in flies. Multitissue transcriptional changes and concomitant metabolic responses to acute CR have not been described. We generated whole genome RNA transcript profiles in liver, skeletal muscle, colon, and hypothalamus and simultaneously measured plasma metabolites using proton nuclear magnetic resonance in mice subjected to acute CR. Liver and muscle showed increased gene expressions associated with fatty acid metabolism and a reduction in those involved in hepatic lipid biosynthesis. Glucogenic amino acids increased in plasma, and gene expression for hepatic gluconeogenesis was enhanced. Increased expression of genes for hormone-mediated signaling and decreased expression of genes involved in protein binding and development occurred in hypothalamus. Cell proliferation genes were decreased and cellular transport genes increased in colon. Acute CR captured many, but not all, hepatic transcriptional changes of long-term CR. Our findings demonstrate a clear transcriptional response across multiple tissues during acute CR, with congruent plasma metabolite changes. Liver and muscle switched gene expression away from energetically expensive biosynthetic processes toward energy conservation and utilization processes, including fatty acid metabolism and gluconeogenesis. Both muscle and colon switched gene expression away from cellular proliferation. Mice undergoing acute CR rapidly adopt many transcriptional and metabolic changes of long-term CR, suggesting that the beneficial effects of CR may require only a short-term reduction in caloric intake.

scholarly journals Nickel-induced transcriptional changes persist  post exposure through epigenetic reprogramming

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Cynthia C. Jose ◽  
Zhenjia Wang ◽  
Vinay Singh Tanwar ◽  
Xiaoru Zhang ◽  
Chongzhi Zang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modification ◽  
Lung Epithelial Cells ◽  
Differentially Expressed ◽  
Nickel Ions ◽  
Post Exposure ◽  
Genome Wide ◽  
Transcriptional Changes ◽  
Nickel Exposure

Abstract Background Nickel is an occupational and environmental toxicant associated with a number of diseases in humans including pulmonary fibrosis, bronchitis and lung and nasal cancers. Our earlier studies showed that the nickel-exposure-induced genome-wide transcriptional changes, which persist even after the termination of exposure may underlie nickel pathogenesis. However, the mechanisms that drive nickel-induced persistent changes to the transcriptome remain elusive. Results To elucidate the mechanisms that underlie nickel-induced long-term transcriptional changes, in this study, we examined the transcriptome and the epigenome of human lung epithelial cells during nickel exposure and after the termination of exposure. We identified two categories of persistently differentially expressed genes: (i) the genes that were differentially expressed during nickel exposure; and (ii) the genes that were differentially expressed only after the termination of exposure. Interestingly, > 85% of the nickel-induced gene expression changes occurred only after the termination of exposure. We also found extensive genome-wide alterations to the activating histone modification, H3K4me3, after the termination of nickel exposure, which coincided with the post-exposure gene expression changes. In addition, we found significant post-exposure alterations to the repressive histone modification, H3K27me3. Conclusion Our results suggest that while modest first wave of transcriptional changes occurred during nickel exposure, extensive transcriptional changes occurred during a second wave of transcription for which removal of nickel ions was essential. By uncovering a new category of transcriptional and epigenetic changes, which occur only after the termination of exposure, this study provides a novel understanding of the long-term deleterious consequences of nickel exposure on human health.

scholarly journals Transcriptional signatures throughout development: the effects of mouse embryo manipulation in vitro

Reproduction ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. 107-122 ◽  
Author(s):  
Sky K Feuer ◽  
Xiaowei Liu ◽  
Annemarie Donjacour ◽  
Rhodel Simbulan ◽  
Emin Maltepe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Preimplantation Embryo ◽  
Environmental Exposures ◽  
Developmental Time ◽  
Transcriptional Responses ◽  
Transcriptional Changes ◽  
Specific Impact

Stressful environmental exposures incurred early in development can affect postnatal metabolic health and susceptibility to non-communicable diseases in adulthood, although the molecular mechanisms by which this occurs have yet to be elucidated. Here, we use a mouse model to investigate how assortedin vitroexposures restricted exclusively to the preimplantation period affect transcription both acutely in embryos and long term in subsequent offspring adult tissues, to determine if reliable transcriptional markers ofin vitrostress are present at specific developmental time points and throughout development. Eachin vitrofertilization or embryo culture environment led to a specific and unique blastocyst transcriptional profile, but we identified a common 18-gene and 9-pathway signature of preimplantation embryo manipulation that was present in allin vitroembryos irrespective of culture condition or method of fertilization. This fingerprint did not persist throughout development, and there was no clear transcriptional cohesion between adult IVF offspring tissues or compared to their preceding embryos, indicating a tissue-specific impact ofin vitrostress on gene expression. However, the transcriptional changes present in each IVF tissue were targeted by the same upstream transcriptional regulators, which provide insight as to how acute transcriptional responses to stressful environmental exposures might be preserved throughout development to influence adult gene expression.

scholarly journals Transcriptional changes before and after forgetting of a long-term sensitization memory in Aplysia californica

2018 ◽  
Vol 155 ◽  
pp. 474-485
Author(s):  
Ushma Patel ◽  
Leticia Perez ◽  
Steven Farrell ◽  
Derek Steck ◽  
Athira Jacob ◽  
...  
Keyword(s):  
Aplysia Californica ◽  
Before And After ◽  
Transcriptional Changes

scholarly journals Mushroom body specific transcriptome analysis reveals dynamic regulation of learning and memory genes after acquisition of long-term courtship memory in Drosophila

2018 ◽  
Author(s):  
Spencer G. Jones ◽  
Kevin C.J. Nixon ◽  
Jamie M. Kramer
Keyword(s):  
Gene Expression ◽  
Learning And Memory ◽  
Transcriptome Analysis ◽  
Mushroom Body ◽  
Neuron Activity ◽  
Specific Gene ◽  
Altered Expression ◽  
Transcriptional Changes ◽  
Memory Acquisition

AbstractThe formation and recall of long-term memory (LTM) requires neuron activity-induced gene expression. Transcriptome analysis has been used to identify genes that have altered expression after memory acquisition, however, we still have an incomplete picture of the transcriptional changes that are required for LTM formation. The complex spatial and temporal dynamics of memory formation creates significant challenges in defining memory-relevant gene expression changes. The mushroom body (MB) is a signaling hub in the insect brain that integrates sensory information to form memories. Here, we performed transcriptome analysis in the Drosophila MB at two time points after the acquisition of LTM: 1 hour and 24 hours. The MB transcriptome was compared to biologically paired whole head (WH) transcriptomes. In both, we identified more transcriptional changes 1 hour after memory acquisition (WH = 322, MB = 302) than at 24 hours (WH = 23, MB = 20). WH samples showed downregulation of developmental genes and upregulation of sensory response genes. In contrast, MB samples showed vastly different gene expression changes affecting biological processes that are specifically related to LTM. MB-downregulated genes were highly enriched for metabolic function, consistent with the MB-specific energy influx that occurs during LTM formation. MB-upregulated genes were highly enriched for known learning and memory processes, including calcium-mediated neurotransmitter release and cAMP signalling. The neuron activity inducible genes hr38 and sr were also specifically induced in the MB. These results highlight the importance of sampling time and cell type in capturing biologically relevant transcriptional changes involved in learning and memory. Our data suggests that MB cells transiently upregulate known memory-related pathways after memory acquisition and provides a critical frame of reference for further investigation into the role of MB-specific gene regulation in memory.

scholarly journals The impact of light and temperature on chromatin organization and plant adaptation

2020 ◽  
Vol 71 (17) ◽  
pp. 5247-5255 ◽  
Author(s):  
Giorgio Perrella ◽  
Anna Zioutopoulou ◽  
Lauren R Headland ◽  
Eirini Kaiserli
Keyword(s):  
Gene Expression ◽  
Nuclear Architecture ◽  
Chromatin Organization ◽  
Developmental Trajectory ◽  
Plant Adaptation ◽  
Short And Long Term ◽  
Composition Structure ◽  
The Impact

Abstract Light and temperature shape the developmental trajectory and morphology of plants. Changes in chromatin organization and nuclear architecture can modulate gene expression and lead to short- and long-term plant adaptation to the environment. Here, we review recent reports investigating how changes in chromatin composition, structure, and topology modulate gene expression in response to fluctuating light and temperature conditions resulting in developmental and physiological responses. Furthermore, the potential application of novel revolutionary techniques, such Hi-C, RNA fluorescence in situ hybridization (FISH) and padlock-FISH, to study the impact of environmental stimuli such as light and temperature on nuclear compartmentalization in plants is discussed.

scholarly journals A predictive model of gene expression reveals the role of network motifs in the mating response of yeast

2021 ◽  
Vol 14 (670) ◽  
pp. eabb5235 ◽  
Author(s):  
Amy E. Pomeroy ◽  
Matthew I. Peña ◽  
John R. Houser ◽  
Gauri Dixit ◽  
Henrik G. Dohlman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Network Motifs ◽  
Mating Response ◽  
Architectural Elements ◽  
Genetic Perturbations ◽  
Transcriptional Changes ◽  
Parameterized Model

Cells use signaling pathways to receive and process information about their environment. These nonlinear systems rely on feedback and feedforward regulation to respond appropriately to changing environmental conditions. Mathematical models describing signaling pathways often lack predictive power because they are not trained on data that encompass the diverse time scales on which these regulatory mechanisms operate. We addressed this limitation by measuring transcriptional changes induced by the mating response in Saccharomyces cerevisiae exposed to different dynamic patterns of pheromone. We found that pheromone-induced transcription persisted after pheromone removal and showed long-term adaptation upon sustained pheromone exposure. We developed a model of the regulatory network that captured both characteristics of the mating response. We fit this model to experimental data with an evolutionary algorithm and used the parameterized model to predict scenarios for which it was not trained, including different temporal stimulus profiles and genetic perturbations to pathway components. Our model allowed us to establish the role of four architectural elements of the network in regulating gene expression. These network motifs are incoherent feedforward, positive feedback, negative feedback, and repressor binding. Experimental and computational perturbations to these network motifs established a specific role for each in coordinating the mating response to persistent and dynamic stimulation.

scholarly journals Time-course analysis of the effect of embedded metal on skeletal muscle gene expression

2020 ◽  
Vol 52 (12) ◽  
pp. 575-587
Author(s):  
Yuan Wen ◽  
Ivan J. Vechetti ◽  
Alexander P. Alimov ◽  
Jessica F. Hoffman ◽  
Vernieda B. Vergara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Heavy Metal ◽  
Muscle Tissue ◽  
Skeletal Muscle Tissue ◽  
Surgical Removal ◽  
Muscle Gene Expression ◽  
Transcriptional Changes ◽  
Muscle Gene

As a consequence of military operations, many veterans suffer from penetrating wounds and long-term retention of military-grade heavy metal fragments. Fragments vary in size and location, and complete surgical removal may not be feasible or beneficial in all cases. Increasing evidence suggests retention of heavy metal fragments may have serious biological implications, including increased risks for malignant transformation. Previous studies assessed the tumorigenic effects of metal alloys in rats, demonstrating combinations of metals are sufficient to induce tumor formation after prolonged retention in skeletal muscle tissue. In this study, we analyzed transcriptional changes in skeletal muscle tissue in response to eight different military-relevant pure metals over 12 mo. We found that most transcriptional changes occur at 1 and 3 mo after metal pellets are embedded in skeletal muscle and these effects resolve at 6 and 12 mo. We also report significant immunogenic effects of nickel and cobalt and suppressive effects of lead and depleted uranium on gene expression. Overall, skeletal muscle exhibits a remarkable capacity to adapt to and recover from internalized metal fragments; however, the cellular response to chronic exposure may be restricted to the metal-tissue interface. These data suggest that unless affected regions are specifically captured by biopsy, it would be difficult to reliably detect changes in muscle gene expression that would be indicative of long-term adverse health outcomes.

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