scholarly journals Sex Differences in Liver, Adipose Tissue, and Muscle Transcriptional Response to Fasting and Refeeding in Mice

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1529
Author(s):  
Nadezhda Bazhan ◽  
Tatiana Jakovleva ◽  
Natalia Feofanova ◽  
Elena Denisova ◽  
Anastasia Dubinina ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Metabolic Response ◽  
Transcriptional Response ◽  
Acid Oxidation ◽  
Refeeding Syndrome ◽  
Transcriptional Responses ◽  
Hepatic Expression ◽  
Fasting And Refeeding ◽  
Sex Asymmetry

Fasting is often used for obesity correction but the “refeeding syndrome” limits its efficiency, and molecular mechanisms underlying metabolic response to different food availability are under investigation. Sex was shown to affect hormonal and metabolic reactions to fasting/refeeding. The aim of this study was to evaluate hormonal and transcriptional responses to fasting and refeeding in male and female C57Bl/6J mice. Sex asymmetry was observed both at the hormonal and transcriptional levels. Fasting (24 h) induced increase in hepatic Fgf21 gene expression, which was associated with elevation of plasma FGF21 and adiponectin levels, and the upregulation of expression of hepatic (Pparα, Cpt1α) and muscle (Cpt1β, Ucp3) genes involved in fatty acid oxidation. These changes were more pronounced in females. Refeeding (6 h) evoked hyperinsulinemia and increased hepatic expression of gene related to lipogenesis (Fasn) only in males and hyperleptinemia and increase in Fgf21 gene expression in muscles and adipose tissues only in females. The results suggest that in mice, one of the molecular mechanisms underlying sex asymmetry in hepatic Pparα, Cpt1α, muscle Cpt1β, and Ucp3 expression during fasting is hepatic Fgf21 expression, and the reason for sex asymmetry in hepatic Fasn expression during refeeding is male-specific hyperinsulinemia.

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 Multiple Pathways Differentially Regulate Global Oxidative Stress Responses in Fission Yeast

2008 ◽  
Vol 19 (1) ◽  
pp. 308-317 ◽  
Author(s):  
Dongrong Chen ◽  
Caroline R.M. Wilkinson ◽  
Stephen Watt ◽  
Christopher J. Penkett ◽  
W. Mark Toone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Hydrogen Peroxide ◽  
Oxidative Damage ◽  
Stress Responses ◽  
Zinc Finger Protein ◽  
Transcriptional Response ◽  
Minor Role ◽  
Transcriptional Responses ◽  
Regulatory Pathways

Cellular protection against oxidative damage is relevant to ageing and numerous diseases. We analyzed the diversity of genome-wide gene expression programs and their regulation in response to various types and doses of oxidants in Schizosaccharomyces pombe. A small core gene set, regulated by the AP-1–like factor Pap1p and the two-component regulator Prr1p, was universally induced irrespective of oxidant and dose. Strong oxidative stresses led to a much larger transcriptional response. The mitogen-activated protein kinase (MAPK) Sty1p and the bZIP factor Atf1p were critical for the response to hydrogen peroxide. A newly identified zinc-finger protein, Hsr1p, is uniquely regulated by all three major regulatory systems (Sty1p-Atf1p, Pap1p, and Prr1p) and in turn globally supports gene expression in response to hydrogen peroxide. Although the overall transcriptional responses to hydrogen peroxide and t-butylhydroperoxide were similar, to our surprise, Sty1p and Atf1p were less critical for the response to the latter. Instead, another MAPK, Pmk1p, was involved in surviving this stress, although Pmk1p played only a minor role in regulating the transcriptional response. These data reveal a considerable plasticity and differential control of regulatory pathways in distinct oxidative stress conditions, providing both specificity and backup for protection from oxidative damage.

scholarly journals Altered Genes and Biological Functions in Response to Severe Burns

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Xinheng Liu ◽  
Yongxian Rong ◽  
Donglin Huang ◽  
Zhijie Liang ◽  
Xiaolin Yi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Roc Curve ◽  
Molecular Mechanisms ◽  
Metabolic Response ◽  
Heat Exposure ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Ppi Network ◽  
Gene Set ◽  
Severe Burns

Severe burns are acute wounds caused by local heat exposure, resulting in life-threatening systemic effects and poor survival. However, the specific molecular mechanisms remain unclear. First, we downloaded gene expression data related to severe burns from the GEO database (GSE19743, GSE37069, and GSE77791). Then, a gene expression analysis was performed to identify differentially expressed genes (DEGs) and construct protein-protein interaction (PPI) network. The molecular mechanism was identified by enrichment analysis and Gene Set Enrichment Analysis. In addition, STEM software was used to screen for genes persistently expressed during response to severe burns, and receiver operating characteristic (ROC) curve was used to identify key DEGs. A total of 2631 upregulated and 3451 downregulated DEGs were identified. PPI network analysis clustered these DEGs into 13 modules. Importantly, module genes mostly related with immune responses and metabolism. In addition, we identified genes persistently altered during the response to severe burns corresponding to survival and death status. Among the genes with high area under the ROC curve in the PPI network gene, CCL5 and LCK were identified as key DEGs, which may affect the prognosis of burn patients. Gene set variation analysis showed that the immune response was inhibited and several types of immune cells were decreased, while the metabolic response was enhanced. The results showed that persistent gene expression changes occur in response to severe burns, which may underlie chronic alterations in physiological pathways. Identifying the key altered genes may reveal potential therapeutic targets for mitigating the effects of severe burns.

scholarly journals Patterns of parent and offspring gene expression reflect canalization, not plasticity, in response to environmental stress

2021 ◽  
Author(s):  
Jeanette B Moss ◽  
Christopher B Cunningham ◽  
Elizabeth C McKinney ◽  
Allen J. Moore
Keyword(s):  
Gene Expression ◽  
Environmental Change ◽  
Environmental Stress ◽  
Behavioral Plasticity ◽  
Transcriptional Response ◽  
Transcriptional Responses ◽  
Behavioral Stability ◽  
The Face ◽  
Transcriptional Changes ◽  
Hostile Environments

Parenting buffers offspring from hostile environments, but it is not clear how or if the genes that underlie parenting change their expression under environmental stress. We recently demonstrated that for the subsocial carrion beetle, Nicrophorus orbicollis, temperature during parenting does not affect parenting phenotypes. Here, we ask if transcriptional changes associated with parenting are likewise robust to environmental stress. The absence of a transcriptional response for parenting under stress would suggest that the genetic programs for parenting and being parented are canalized. Conversely, a robust transcriptional response would suggest that plasticity of underlying gene expression is critical for maintaining behavioral stability, and that these mechanisms provide a potential target for selection in the face of environmental change. We test these alternatives by characterizing gene expression of parents and offspring with and without parent-offspring interactions under a benign and a stressful temperature. We found that parent-offspring interactions elicit distinct transcriptional responses of parents and larvae irrespective of temperature. We further detected robust changes of gene expression in beetles breeding at 24 degrees C compared to 20 degrees C irrespective of family interaction. However, no strong interaction between parent-offspring interaction and temperature was detected for either parents or larvae. We therefore conclude that canalization, not plasticity of gene expression, most likely explains the absence of behavioral plasticity under thermal stress. This result suggests that species may not have the genetic variation needed to respond to all environmental change, especially for complex phenotypes.

scholarly journals Pneumolysin is responsible for differential gene expression and modifications in the epigenetic landscape of primary monocyte derived macrophages

2020 ◽  
Author(s):  
J. Cole ◽  
A. Angyal ◽  
R. D. Emes ◽  
T.J. Mitchell ◽  
M.J. Dickman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Immune Responses ◽  
Epigenetic Modification ◽  
Transcriptional Response ◽  
Innate Immune ◽  
Global Changes ◽  
Innate Immune Responses ◽  
Transcriptional Responses ◽  
Tnf Α

AbstractEpigenetic modifications regulate gene expression in the host response to a diverse range of pathogens. The extent and consequences of epigenetic modification during macrophage responses to Streptococcus pneumoniae, and the role of pneumolysin, a key Streptococcus pneumoniae virulence factor, in influencing these responses, are currently unknown. To investigate this, we infected human monocyte derived macrophages (MDMs) with Streptococcus pneumoniae and addressed whether pneumolysin altered the epigenetic landscape and the associated acute macrophage transcriptional response using a combined transcriptomic and proteomic approach. Transcriptomic analysis identified 503 genes that were differentially expressed in a pneumolysin-dependent manner in these samples. Pathway analysis highlighted the involvement of transcriptional responses to core innate responses to pneumococci including modules associated with metabolic pathways activated in response to infection, oxidative stress responses and NFκB, NOD-like receptor and TNF signalling pathways. Quantitative proteomic analysis confirmed pneumolysin-regulated protein expression, early after bacterial challenge, in representative transcriptional modules associated with innate immune responses. In parallel, quantitative mass spectrometry identified global changes in the relative abundance of histone post translational modifications (PTMs) upon pneumococcal challenge. We identified an increase in the relative abundance of H3K4me1, H4K16ac and a decrease in H3K9me2 and H3K79me2 in a PLY-dependent fashion. We confirmed that pneumolysin blunted early transcriptional responses involving TNF-α and IL-6 expression. Vorinostat, a histone deacetylase inhibitor, similarly downregulated TNF production, reprising the pattern observed with pneumolysin. In conclusion, widespread changes in the macrophage transcriptional response are regulated by pneumolysin and are associated with global changes in histone PTMs. Modulating histone PTMs can reverse pneumolysin-associated transcriptional changes influencing innate immune responses, suggesting that epigenetic modification by pneumolysin plays a role in dampening the innate responses to pneumococci.Author summaryPneumolysin is a toxin that contributes to how Streptococcus pneumoniae, the leading cause of pneumonia, causes disease. In this study, the toxin alters gene expression in immune cells called macrophages, one of the first lines of defence against bacteria at sites of infection. Modulation involved multiple immune responses, including generation of chemical signals coordinating responses in immune cells termed cytokines. In addition, changes were observed in histone proteins that are involved in controlling gene expression in the cell. Pneumolysin reduced early production of the cytokine TNF-α and a medicine vorinostat that modifies these ‘epigenetic’ histone modifications had a similar affect, suggesting epigenetic mechanisms contribute to the ability of pneumolysin to reduce immune responses.

scholarly journals Changes in DnaA-Dependent Gene Expression Contribute to the Transcriptional and Developmental Response of Bacillus subtilis to Manganese Limitation in Luria-Bertani Medium

2010 ◽  
Vol 192 (15) ◽  
pp. 3915-3924 ◽  
Author(s):  
Sharon E. Hoover ◽  
Weihong Xu ◽  
Wenzhong Xiao ◽  
William F. Burkholder
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Bacillus Subtilis ◽  
Dna Replication ◽  
Alkylating Agents ◽  
Transcriptional Response ◽  
Sos Response ◽  
Replication Initiation ◽  
Specific Gene ◽  
Transcriptional Responses

ABSTRACT The SOS response to DNA damage in bacteria is a well-known component of the complex transcriptional responses to genotoxic environmental stresses such as exposure to reactive oxygen species, alkylating agents, and many of the antibiotics targeting DNA replication. However, bacteria such as Bacillus subtilis also respond to conditions that perturb DNA replication via a transcriptional response mediated by the replication initiation protein DnaA. In addition to regulating the initiation of DNA replication, DnaA directly regulates the transcription of specific genes. Conditions that perturb DNA replication can trigger the accumulation of active DnaA, activating or repressing the transcription of genes in the DnaA regulon. We report here that simply growing B. subtilis in LB medium altered DnaA-dependent gene expression in a manner consistent with the accumulation of active DnaA and that this was part of a general transcriptional response to manganese limitation. The SOS response to DNA damage was not induced under these conditions. One of the genes positively regulated by DnaA in Bacillus subtilis encodes a protein that inhibits the initiation of sporulation, Sda. Sda expression was induced as cells entered stationary phase in LB medium but not in LB medium supplemented with manganese, and the induction of Sda inhibited sporulation-specific gene expression and the onset of spore morphogenesis. In the absence of Sda, manganese-limited cells initiated spore development but failed to form mature spores. These data highlight that DnaA-dependent gene expression may influence the response of bacteria to a range of environmental conditions, including conditions that are not obviously associated with genotoxic stress.

scholarly journals MicroRNA-Mediated Regulation of Initial Host Responses in a Symbiotic Organ

mSystems ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Silvia Moriano-Gutierrez ◽  
Edward G. Ruby ◽  
Margaret J. McFall-Ngai
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Tissue Remodeling ◽  
Mrna Translation ◽  
Functional Enrichment ◽  
Critical Event ◽  
Light Organ ◽  
Transcriptional Responses ◽  
Mrna Targets ◽  
Host Tissues

ABSTRACT One of the most important events in an animal’s life history is the initial colonization by its microbial symbionts, yet little is known about this event’s immediate impacts on the extent of host gene expression or the molecular mechanisms controlling it. MicroRNAs (miRNAs) are short, noncoding RNAs that bind to target mRNAs, rapidly shaping gene expression by posttranscriptional control of mRNA translation and decay. Here, we show that, in the experimentally tractable binary squid-vibrio symbiosis, colonization of the light organ induces extensive changes in the miRNA transcriptome. Examination of the squid genome revealed the presence of evolutionarily conserved genes encoding elements essential for the production and processing of miRNAs. At 24 h postcolonization, 215 host miRNAs were detected in the light organ, 26 of which were differentially expressed in response to the symbionts. A functional enrichment analysis of genes potentially targeted by downregulation of certain miRNAs at the initiation of symbiosis revealed two major gene ontology (GO) term categories, neurodevelopment and tissue remodeling. This symbiont-induced downregulation is predicted to promote these activities in host tissues and is consistent with the well-described tissue remodeling that occurs at the onset of the association. Conversely, predicted targets of upregulated miRNAs, including the production of mucus, are consistent with attenuation of immune responses by symbiosis. Taken together, our data provide evidence that, at the onset of symbiosis, host miRNAs in the light organ drive alterations in gene expression that (i) orchestrate the symbiont-induced development of host tissues, and (ii) facilitate the partnership by dampening the immune response. IMPORTANCE Animals often acquire their microbiome from the environment at each generation, making the initial interaction of the partners a critical event in the establishment and development of a stable, healthy symbiosis. However, the molecular nature of these earliest interactions is generally difficult to study and poorly understood. We report that, during the initial 24 h of the squid-vibrio association, a differential expression of host miRNAs is triggered by the presence of the microbial partner. Predicted mRNA targets of these miRNAs were associated with regulatory networks that drive tissue remodeling and immune suppression, two major symbiosis-induced developmental outcomes in this and many other associations. These results implicate regulation by miRNAs as key to orchestrating the critical transcriptional responses that occur very early during the establishment of a symbiosis. Animals with more complex microbiota may have similar miRNA-driven responses as their association is initiated, supporting an evolutionary conservation of symbiosis-induced developmental mechanisms.

scholarly journals Diversity of microglial transcriptional responses during opioid exposure and neuropathic pain

2021 ◽  
Author(s):  
Elizabeth I Sypek ◽  
Hannah Y Collins ◽  
William M McCallum ◽  
Alexandra T Bourdillon ◽  
Christopher J Bohlen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Microglial Activation ◽  
Molecular Mechanisms ◽  
Transcriptional Response ◽  
Morphine Treatment ◽  
Transcriptional Responses ◽  
Opioid Treatment ◽  
Functional Studies ◽  
Opioid Induced Hyperalgesia ◽  
Histological Data

Microglia take on an altered morphology during chronic opioid treatment. This morphological change is broadly used to identify the activated microglial state associated with opioid side effects, including tolerance and opioid-induced hyperalgesia (OIH). Following chronic opioid treatment and peripheral nerve injury (PNI) microglia in the spinal cord display similar morphological responses. Consistent with this observation, functional studies have suggested that microglia activated by PNI or opioids engage common molecular mechanisms to induce hypersensitivity. Here we conducted deep RNA sequencing of acutely isolated spinal cord microglia from male mice to comprehensively interrogate transcriptional states and mechanistic commonality between multiple OIH and PNI models. Following PNI, we identify a common early proliferative transcriptional event across models that precedes the upregulation of histological markers of activation, followed by a delayed and injury-specific transcriptional response. Strikingly, we found no such transcriptional responses associated with opioid-induced microglial activation, consistent with histological data indicating that microglia number remain stable during morphine treatment. Collectively, these results reveal the diversity of pain-associated microglial transcriptomes and point towards the targeting of distinct insult-specific microglial responses to treat OIH, PNI, or other CNS pathologies.

scholarly journals Glucose and glutamine availability regulate HepG2 transcriptional responses to low oxygen

2018 ◽  
Vol 3 ◽  
pp. 126 ◽  
Author(s):  
Alvina G. Lai ◽  
Donall Forde ◽  
Wai Hoong Chang ◽  
Fang Yuan ◽  
Xiaodong Zhuang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mass Spectrometry ◽  
Transcriptional Response ◽  
Global Changes ◽  
Low Oxygen ◽  
Transcriptional Responses ◽  
Dna Hydroxymethylation ◽  
Modified Dna ◽  
The Impact

Background: Little is known about the impact of nutrients on cellular transcriptional responses, especially in face of environmental stressors such as oxygen deprivation. Hypoxia-inducible factors (HIF) coordinate the expression of genes essential for adaptation to oxygen-deprived environments. A second family of oxygen-sensing genes known as the alpha-ketoglutarate-dependent dioxygenases are also implicated in oxygen homeostasis and epigenetic regulation. The relationship between nutritional status and cellular response to hypoxia is understudied. In vitro cell culture systems frequently propagate cells in media that contains excess nutrients, and this may directly influence transcriptional response in hypoxia. Methods: We studied the effect of glucose and glutamine concentration on HepG2 hepatoma transcriptional response to low oxygen and expression of hypoxia inducible factor-1α (HIF-1α). Mass spectrometry confirmed low oxygen perturbation of dioxygenase transcripts resulted in changes in DNA methylation. Results: Under normoxic conditions, we observed a significant upregulation of both HIF-target genes and oxygen-dependent dioxygenases in HepG2 cells cultured with physiological levels of glucose or glutamine relative to regular DMEM media, demonstrating that excess glutamine/glucose can mask changes in gene expression. Under hypoxic conditions, CA9 was the most upregulated gene in physiological glutamine media while TETs and FTO dioxygenases were downregulated in physiological glucose. Hypoxic regulation of these transcripts did not associate with changes in HIF-1α protein expression. Downregulation of TETs suggests a potential for epigenetic modulation. Mass-spectrometry quantification of modified DNA bases confirmed our transcript data. Hypoxia resulted in decreased DNA hydroxymethylation, which correlated with TETs downregulation. Additionally, we observed that TET2 expression was significantly downregulated in patients with hepatocellular carcinoma, suggesting that tumour hypoxia may deregulate TET2 expression resulting in global changes in DNA hydroxymethylation.   Conclusion: Given the dramatic effects of nutrient availability on gene expression, future in vitro experiments should be aware of how excess levels of glutamine and glucose may perturb transcriptional responses.

scholarly journals Global Transcriptional Responses to Osmotic, Oxidative, and Imipenem Stress Conditions in Pseudomonas putida

2017 ◽  
Vol 83 (7) ◽  
Author(s):  
Klara Bojanovič ◽  
Isotta D'Arrigo ◽  
Katherine S. Long
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Pseudomonas Putida ◽  
Cellular Response ◽  
Functional Characterization ◽  
Transcriptional Response ◽  
Stress Conditions ◽  
Differentially Expressed ◽  
Transcriptional Responses ◽  
Content Type

ABSTRACTBacteria cope with and adapt to stress by modulating gene expression in response to specific environmental cues. In this study, the transcriptional response ofPseudomonas putidaKT2440 to osmotic, oxidative, and imipenem stress conditions at two time points was investigated via identification of differentially expressed mRNAs and small RNAs (sRNAs). A total of 440 sRNA transcripts were detected, of which 10% correspond to previously annotated sRNAs, 40% to novel intergenic transcripts, and 50% to novel transcripts antisense to annotated genes. Each stress elicits a unique response as far as the extent and dynamics of the transcriptional changes. Nearly 200 protein-encoding genes exhibited significant changes in all stress types, implicating their participation in a general stress response. Almost half of the sRNA transcripts were differentially expressed under at least one condition, suggesting possible functional roles in the cellular response to stress conditions. The data show a larger fraction of differentially expressed sRNAs than of mRNAs with >5-fold expression changes. The work provides detailed insights into the mechanisms through whichP. putidaresponds to different stress conditions and increases understanding of bacterial adaptation in natural and industrial settings.IMPORTANCEThis study maps the complete transcriptional response ofP. putidaKT2440 to osmotic, oxidative, and imipenem stress conditions at short and long exposure times. Over 400 sRNA transcripts, consisting of both intergenic and antisense transcripts, were detected, increasing the number of identified sRNA transcripts in the strain by a factor of 10. Unique responses to each type of stress are documented, including both the extent and dynamics of the gene expression changes. The work adds rich detail to previous knowledge of stress response mechanisms due to the depth of the RNA sequencing data. Almost half of the sRNAs exhibit significant expression changes under at least one condition, suggesting their involvement in adaptation to stress conditions and identifying interesting candidates for further functional characterization.

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