Correction: Rapid Changes in Gene Expression Dynamics in Response to Superoxide Reveal SoxRS-Dependent and Independent Transcriptional Networks
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PROVIDER: S-EPMC3525699 | biostudies-literature | 2012 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundSoxR and SoxS constitute an intracellular signal response system that rapidly detects changes in superoxide levels and modulates gene expression in E. coli. A time series microarray design was used to identify co-regulated SoxRS-dependent and independent genes modulated by superoxide minutes after exposure to stress.Methodology/principal findingssoxS mRNA levels surged to near maximal levels within the first few minutes of exposure to paraquat, a superoxide-producing compound, followed by a rise in mRNA levels of known SoxS-regulated genes. Based on a new method for determining the biological significance of clustering results, a total of 138 genic regions, including several transcription factors and putative sRNAs were identified as being regulated through the SoxRS signaling pathway within 10 minutes of paraquat treatment. A statistically significant two-block SoxS motif was identified through analysis of the SoxS-regulated genes. The SoxRS-independent response included members of the OxyR, CysB, IscR, BirA and Fur regulons. Finally, the relative sensitivity to superoxide was measured in 94 strains carrying deletions in individual, superoxide-regulated genes.Conclusions/significanceBy integrating our microarray time series results with other microarray data, E. coli databases and the primary literature, we propose a model of the primary transcriptional response containing 226 protein-coding and sRNA sequences. From the SoxS dependent network the first statistically significant SoxS-related motif was identified.
| S-EPMC2064960 | biostudies-literature
Project description:BackgroundHigh concentrations of reactive oxygen species (ROS) were reported to cause oxidative stress to E. coli cells associated with reduced or inhibited growth. The high ROS concentrations described in these reports were generated by exposing the bacteria to H2O2 and superoxide-generating chemicals which are non-physiological growth conditions. However, the effect of molecular oxygen on oxidative stress response has not been evaluated. Since the use of oxygen-enriched air is a common strategy to support high density growth of E. coli, it was important to investigate the effect of high dissolved oxygen concentrations on the physiology and growth of E. coli and the way it responds to oxidative stress.ResultsTo determine the effect of elevated oxygen concentrations on the growth characteristics, specific gene expression and enzyme activity in E. coli, the parental and SOD-deficient strain were evaluated when the dissolved oxygen (dO2) level was increased from 30% to 300%. No significant differences in the growth parameters were observed in the parental strain except for a temporary decrease of the respiration and acetate accumulation profile. By performing transcriptional analysis, it was determined that the parental strain responded to the oxidative stress by activating the SoxRS regulon. However, following the dO2 switch, the SOD-deficient strain activated both the SoxRS and OxyR regulons but it was unable to resume its initial growth rate.ConclusionThe transcriptional analysis and enzyme activity results indicated that when E. coli is exposed to dO2 shift, the superoxide stress regulator SoxRS is activated and causes the stimulation of the superoxide dismutase system. This enables the E. coli to protect itself from the poisoning effects of oxygen. The OxyR protecting system was not activated, indicating that H2O2 did not increase to stressing levels.
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Project description:When Escherichia coli is exposed to redox-cycling drugs, its SoxR transcription factor is activated by oxidation of its [2Fe-2S] cluster. In aerobic cells these drugs generate superoxide, and because superoxide dismutase (SOD) is a member of the SoxRS regulon, superoxide was initially thought to be the activator of SoxR. Its many-gene regulon was therefore believed to comprise a defence against superoxide stress. However, we found that abundant superoxide did not effectively activate SoxR in an SOD⁻ mutant, that overproduced SOD could not suppress activation by redox-cycling drugs, and that redox-cycling drugs were able to activate SoxR in anaerobic cells as long as alternative respiratory acceptors were provided. Thus superoxide is not the signal that SoxR senses. Indeed, redox-cycling drugs directly oxidized the cluster of purified SoxR in vitro, while superoxide did not. Redox-cycling drugs are excreted by both bacteria and plants. Their toxicity does not require superoxide, as they poisoned E. coli under anaerobic conditions, in part by oxidizing dehydratase iron-sulfur clusters. Under these conditions SoxRS induction was protective. Thus it is physiologically appropriate that the SoxR protein directly senses redox-cycling drugs rather than superoxide.
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Project description:Active enhancers of the human genome generate long noncoding transcripts known as enhancer RNAs (eRNAs). How dynamic transcriptional changes of eRNAs are physically and functionally linked with target gene transcription remains unclear. To investigate the dynamic functional relationships among eRNAs and target promoters, we obtained a dense time series of GRO-seq and ChIP-seq data to generate a time-resolved enhancer activity map of a cell undergoing an innate antiviral immune response. Dynamic changes in eRNA and pre-mRNA transcription activities suggest distinct regulatory roles of enhancers. Using a criterion based on proximity and transcriptional inducibility, we identified 123 highly confident pairs of virus-inducible enhancers and their target genes. These enhancers interact with their target promoters transiently and concurrently at the peak of gene activation. Accordingly, their physical disassociation from the promoters is likely involved in post-induction repression. Functional assessments further establish that these eRNAs are necessary for full induction of the target genes and that a complement of inducible eRNAs functions together to achieve full activation. Lastly, we demonstrate the potential for eRNA-targeted transcriptional reprogramming through targeted reduction of eRNAs for a clinically relevant gene, TNFSF10, resulting in a selective control of interferon-induced apoptosis.
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2015-08-13 | GSE65712 | GEO
Project description:Plant growth adjustment during water deficit is a crucial adaptive response. The rapid fine-tuned control achieved at the post-translational level is believed to be of considerable importance for regulating early changes in plant growth reprogramming. Aiming at a better understanding of early responses to contrasting plant water statuses, we carried out a survey of the protein phosphorylation events in the growing zone of maize leaves upon a range of water regimes. In this study, the impact of mild and severe water deficits were evaluated in comparison with constant optimal watering and with recovery periods lasting 5, 10, 20, 30, 45, and 60 min. Using four biological replicates per treatment and a robust quantitative phosphoproteomic methodology based on stable-isotope labeling, we identified 3664 unique phosphorylation sites on 2496 proteins. The abundance of nearly 1250 phosphorylated peptides was reproducibly quantified and profiled with high confidence among treatments. A total of 138 phosphopeptides displayed highly significant changes according to water regimes and enabled to identify specific patterns of response to changing plant water statuses. Further quantification of protein amounts emphasized that most phosphorylation changes did not reflect protein abundance variation. During water deficit and recovery, extensive changes in phosphorylation status occurred in critical regulators directly or indirectly involved in plant growth and development. These included proteins influencing epigenetic control, gene expression, cell cycle-dependent processes and phytohormone-mediated responses. Some of the changes depended on stress intensity whereas others depended on rehydration duration, including rapid recoveries that occurred as early as 5 or 10 mins after rewatering. By combining a physiological approach and a quantitative phosphoproteomic analysis, this work provides new insights into the in vivo early phosphorylation events triggered by rapid changes in plant water status, and their possible involvement in plant growth-related processes.
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Project description:The BET family protein BRD4, which forms the CDK9-containing BRD4-PTEFb complex, is considered to be a master regulator of RNA polymerase II (Pol II) pause release. Because its tandem bromodomains interact with acetylated histone lysine residues, it has long been thought that BRD4 requires these bromodomains for its recruitment to chromatin and transcriptional regulatory function. Here, using rapid depletion and genetic complementation with domain deletion mutants, we demonstrate that BRD4 bromodomains are dispensable for Pol II pause release. A minimal, bromodomain-less C-terminal BRD4 fragment containing the PTEFb-interacting C-terminal motif (CTM) is instead both necessary and sufficient to mediate Pol II pause release in the absence of full-length BRD4. Although BRD4-PTEFb can associate with chromatin through acetyl recognition, our results indicate that a distinct, active BRD4-PTEFb population functions to regulate transcription independently of bromodomain-mediated chromatin association. These findings may enable more effective pharmaceutical modulation of BRD4-PTEFb activity.
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2015-08-13 | E-GEOD-65712 | biostudies-arrayexpress
Project description:Neurological disease is characterized the by dysfunction of specific neuroanatomical regions. To determine whether region-specific vulnerabilities have a transcriptional basis at cell-type-specific resolution, we analyzed gene expression in mouse oligodendrocytes across various brain regions. Oligodendrocyte transcriptomes cluster in an anatomical arrangement along the rostrocaudal axis. Moreover, regional oligodendrocyte populations preferentially regulate genes implicated in diseases that target their region of origin. Systems-level analyses identify five region-specific co-expression networks representing distinct molecular pathways in oligodendrocytes. The cortical network exhibits alterations in mouse models of intellectual disability and epilepsy, the cerebellar network in ataxia, and the spinal network in multiple sclerosis. Bioinformatic analyses reveal potential molecular regulators of these networks, which were confirmed to modulate network expression in vitro in human oligodendroglioma cells, including reversal of the disease-associated transcriptional effects of a pathogenic Spinocerebellar ataxia type 1 allele. These findings identify targetable region-specific vulnerabilities to neurological disease mediated by oligodendrocytes.
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