Reinforcement of transcriptional silencing by a positive feedback between DNA methylation and non-coding transcription
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ABSTRACT:
PROVIDER: PRJNA714396 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Non-coding transcription is an important determinant of heterochromatin formation. In Arabidopsis thaliana a specialized RNA polymerase V (Pol V) transcribes pervasively and produces long non-coding RNA. This facilitates locus-specific establishment of RNA-directed DNA methylation (RdDM). Subsequent maintenance of RdDM is associated with elevated levels of Pol V transcription, which is consistent with a mutual reinforcement of DNA methylation and non-coding transcription. However, the impact of DNA methylation on Pol V transcription remained unresolved. We found that loss of DNA methylation leads to a strong reduction of Pol V transcription. This occurs when DNA methylation is lost in all sequence contexts, which may happen not only in mutants defective in RdDM but also in mutants lacking maintenance DNA methyltransferases. Our results support a model where RdDM is maintained by a mutual reinforcement of DNA methylation and Pol V transcription with a strong crosstalk with other silencing pathways.
2021-08-27 | GSE168869 | GEO
Project description: Not available
| S-EPMC8464056 | biostudies-literature
Project description:Analyses of RNAi-heterochromatin positive feedback loop in Tetrahymena
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Project description:The HIF-1α antisense long non-coding RNA drives a positive feedback loop of HIF-1α mediated transactivation and glycolysis
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Project description:Protein translational machinery is an important component of proteostasis network (PN) that maintains cellular proteostasis and regulates aging and other cellular processes. Ample evidence indicates that inhibition of translation initiation factor activities enhances stress resistance and extends life span in model organisms. Eukaryotic translation initiation factor 5B (eIF5B) is responsible for joining of pre-40S subunits with 60S ribosomal subunits to give a 80S-like complex in protein translational initiation and its silencing may disrupt proteostasis and trigger cellular processes associated with stress responses. In the present work, eIF5B was genetically manipulated in 293T cells. The physiological aspects of eIF5B-knockdown cells (eIF5B-KN) were characterized showing that they grew slower, had a lower level of intracellular reactive oxygen species (ROS), an increased resistance to oxidative stress and an enhanced autophagy. Proteomic analysis showed that silencing of eIF5B resulted in up-regulation of 88 proteins and down-regulation of 130 proteins in eIF5B-KN compared to control cells, which involved in diverse cellular processes including metabolism, RNA processing, and protein metabolism, and DNA synthesis. The autonomous downregulation of the MAPK singnaling pathway was identified that led to the prolonged S-phase cell-cycle arrest and contributed to the slow growth of eIF5B-KN cells. Glutamine transporters were found to be downregulated which enhanced formation of autophagy. Furthermore, eIF5B knockdown compromised the integrity of 28S rRNA and 8.5.8S rRNA that can be rescued via restoring the eIF5B expression level. Taken together, these results demonstrated that eIF5B silencing providesd a negative feedback to down regulate the MAPK signaling pathway which reconstitutesd the proteostasis, resulting in a decrease in cell growth and an enhanced resistance to oxidative stress. Our data provide a useful resource to further biological exploration into functions of protein synthesis in regulation of proteostasis and aging and suggest that eIF5B plays a role in aging process.
2017-03-28 | MSV000080711 | MassIVE
Project description:Phospholipase C gamma 1 (PLC-γ1) occupies a critically important position in the T cell signaling pathway. While its functions as a regulator of both Ca2+ signaling and PKC-family kinases are well characterized, PLC-γ1’s role in the regulation of early T cell receptor signaling events is incomplete. Activation of the T cell receptor leads to the formation of a signalosome complex between SLP-76, LAT, PLC-γ1, Itk, and Vav1. Recent studies have revealed the existence of both positive and negative feedback pathways from components of the signalosome complex to the apical kinase in the pathway, Lck. To determine the role, if any, of PLC-γ1 in these feedback networks, we performed a quantitative phosphoproteomic analysis of the PLC-γ1-deficient T cells. These data revealed a previously unappreciated role for PLC-γ1 in the positive regulation of Zap-70 and T cell receptor tyrosine phosphorylation. Conversely, PLC-γ1 negatively regulated the phosphorylation of signalosome associated proteins including previously established Lck substrate phosphorylation sites within this complex. While the positive and negative regulatory phosphorylation sites on Lck were largely unchanged, Tyr192 phosphorylation was elevated in Jgamma1. The data supports a model wherein Lck’s targeting, but not its kinase activity is altered by PLC-γ1, possibly through Lck Tyr192 phosphorylation.
2017-06-28 | PXD005165 | Pride
Project description:Maladaptive Positive Feedback Production of ChREBPβ Drives Glucotoxic β-Cell Failure
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Project description:Successful infection strategies must balance pathogen amplification and persistence. In Toxoplasma gondii, this is accomplished through differentiation into dedicated cyst-forming chronic stages that avoid clearance by the host immune system. The transcription factor BFD1 is both necessary and sufficient for stage conversion; however, its regulation is not understood. We examine five factors transcriptionally activated by BFD1. One of these is a cytosolic RNA-binding protein of the CCCH-type zinc finger family, which we name BFD2. Parasites lacking BFD2 fail to induce BFD1 and are consequently unable to fully differentiate in culture or in mice. BFD2 interacts with the BFD1 transcript under stress and deletion of BFD2 reduces BFD1 protein levels, but not mRNA abundance. The reciprocal effects on BFD2 transcription and BFD1 translation outline a positive feedback loop that enforces commitment to differentiation. BFD2 helps explain how parasites commit to the chronic gene-expression program and elucidates how the balance between proliferation and persistence is achieved over the course of infection.
2023-08-07 | PXD039648 | Pride
Project description:Synthetic systems that use positive feedback have been developed to control human disease vectors and crop pests. The tTAV system, which has been deployed in several insect species, relies on a positive feedback circuit that can be inhibited via dietary tetracycline. Although insects carrying tTAV fail to survive until adulthood in the absence of tetracycline, the exact reason for its lethality, as well as the transcriptomic effects of an active positive feedback circuit, remain unknown. Understanding what factors contribute to the variance in tTAV-associated mortality is likely to inform the development of insect control systems. In the present study, the OXI513a tTAV feedback circuit was introduced and verified into D. melanogaster. The tight tetracycline regulation of the system affords a convenient method to conduct a strain-by-strain assessment of the tTAV system and determine the transcriptomic effect, if any, of a positive feedback circuit. Transcriptomic analysis of four independent D. melanogaster tTAV insertion lines, in both adults and larvae, was conducted to examine the transcriptomic influence of the tTAV system. The tTAV lines and non-tTAV control were maintained on TET-on media for 5 generations prior to commencing. Thirty flies, 15 male and 15 female, of the same age, from each of the strains were transferred to either TET-On or TET-Off media. Five days after transfer, adult flies were removed and 10 adult flies, 5 male & 5 female, were frozen at -80°C. Ten larvae from each of these matings were collected at the late second instar stage, the last life stage normally seen prior to lethality, and frozen at -80°C. Three biological replicates were produced for each combination of strain, life-stage, and media. RNA was prepared from frozen samples using Trizol and DNAse was treated using a PureLink RNA Mini Kit (Invitrogen). Microarray experiments employed Agilent Drosophila Gene Expression Microarrays 4x44K and were scanned on an Agilent G2505C scanner (Agilent Technologies). Data collection was divided into two separate experiments. A pilot experiment for strain 102D consisting of two life stages in two conditions each with three biological replicates – a total of 12 samples. The remaining four strains were run as a separate experiment with a total of 48 samples. For each experiment, sample chip position was randomized to avoid genotype- and treatment-specific batch effects.
2017-12-11 | E-MTAB-6332 | biostudies-arrayexpress
Project description:Protein translational machinery is an important component of proteostasis network (PN) that maintains cellular proteostasis and regulates aging and other cellular processes. Ample evidence indicates that inhibition of translation initiation factor activities enhances stress resistance and extends life span in model organisms. Eukaryotic translation initiation factor 5B (eIF5B) is responsible for joining of pre-40S subunits with 60S ribosomal subunits to give a 80S-like complex in protein translational initiation and its silencing may disrupt proteostasis and trigger cellular processes associated with stress responses. In the present work, eIF5B was genetically manipulated in 293T cells. The physiological aspects of eIF5B-knockdown cells (eIF5B-KN) were characterized showing that they grew slower, had a lower level of intracellular reactive oxygen species (ROS), an increased resistance to oxidative stress and an enhanced autophagy. Proteomic analysis showed that silencing of eIF5B resulted in up-regulation of 88 proteins and down-regulation of 130 proteins in eIF5B-KN compared to control cells, which involved in diverse cellular processes including metabolism, RNA processing, and protein metabolism, and DNA synthesis. The autonomous downregulation of the MAPK singnaling pathway was identified that led to the prolonged S-phase cell-cycle arrest and contributed to the slow growth of eIF5B-KN cells. Glutamine transporters were found to be downregulated which enhanced formation of autophagy. Furthermore, eIF5B knockdown compromised the integrity of 28S rRNA and 8.5.8S rRNA that can be rescued via restoring the eIF5B expression level. Taken together, these results demonstrated that eIF5B silencing providesd a negative feedback to down regulate the MAPK signaling pathway which reconstitutesd the proteostasis, resulting in a decrease in cell growth and an enhanced resistance to oxidative stress. Our data provide a useful resource to further biological exploration into functions of protein synthesis in regulation of proteostasis and aging and suggest that eIF5B plays a role in aging process.
2016-06-13 | PXD003111 | Pride