FOXO-regulated Deaf1 controls muscle regeneration through autophagy
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE237088 | GEO | 2024/05/15
REPOSITORIES: GEO
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Project description:FOXO-regulated Deaf1 controls muscle regeneration through autophagy
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Project description:To study the autophagy related genes, we performed RNAi screens to identify new autophagic regulators. Dwg1 is one of new regulators of autophagy. We hypothesized that as an insulator, the Dwg protein might regulate autophagy through binding to insulator elements on chromatin and blocking enhancer functions. We therefore performed chromatin-immunoprecipitation followed by next-generation sequencing (ChIP-seq) to identify Dwg downstream targets. The results suggest that Dwg binds to the insulator elements present in/near the ATG genes, presumably suppressing their transcription.
2022-12-14 | GSE220887 | GEO
Project description:Drosophila Orb, the homologue of vertebrate CPEB is a key translational regulator involved in oocyte polarity and maturation through poly(A) tail elongation of specific mRNAs. orb has also an essential function during early oogenesis which has not been addressed at the molecular level. Here, we show that orb prevents cell death during early oogenesis, thus allowing oogenesis to progress. It does so through the repression of autophagy, by directly repressing, together with the CCR4 deadenylase, the translation of Autophagy-specific gene 12 (Atg12) mRNA. Autophagy and cell death observed in orb mutant ovaries are reduced by decreasing Atg12 or other Atg mRNA levels. These results reveal a role of Orb in translational repression and identify autophagy as an essential pathway regulated by Orb during early oogenesis. Importantly, they also establish translational regulation as a major mode of control of autophagy, a key process in cell homeostasis in response to environmental cues. Orb RIP-chip vs mock IP on ovaries from mature 3-5 day old females.
2016-07-03 | E-GEOD-74475 | biostudies-arrayexpress
Project description:Drosophila Orb, the homologue of vertebrate CPEB is a key translational regulator involved in oocyte polarity and maturation through poly(A) tail elongation of specific mRNAs. orb has also an essential function during early oogenesis which has not been addressed at the molecular level. Here, we show that orb prevents cell death during early oogenesis, thus allowing oogenesis to progress. It does so through the repression of autophagy, by directly repressing, together with the CCR4 deadenylase, the translation of Autophagy-specific gene 12 (Atg12) mRNA. Autophagy and cell death observed in orb mutant ovaries are reduced by decreasing Atg12 or other Atg mRNA levels. These results reveal a role of Orb in translational repression and identify autophagy as an essential pathway regulated by Orb during early oogenesis. Importantly, they also establish translational regulation as a major mode of control of autophagy, a key process in cell homeostasis in response to environmental cues. Orb RIP-chip vs mock IP on ovaries from newly eclosed females.
2016-07-03 | E-GEOD-74474 | biostudies-arrayexpress
Project description:Minimized combinatorial CRISPR screens identify genetic interactions in autophagy
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Project description:Autophagy involves massive degradation of intracellular components and functions as a conserved system that helps cells to adapt to adverse conditions. In Arabidopsis thaliana, submergence induces the transcription of autophagy-related (ATG) genes and the formation of autophagosomes. To study the role of autophagy during submergence, we performed transcriptome analysis with atg5, an autophagy-defective mutant, under submergence conditions. Our data showed that submergence changed the expression profile of DEG in the atg5 versus wild-type.
2021-09-20 | GSE184340 | GEO
Project description:Chronic CO2 retention, or hypercapnia, occurs in pulmonary diseases and leads to skeletal muscle wasting. Muscle wasting and hypercapnia are independently associated with substantial mortality. While abnormal skeletal muscle stem -satellite- cells, contribute to impaired myogenesis in pulmonary diseases, no mechanistic data exists on hypercapnia-driven dysfunctional satellite cells and myogenesis in-vivo. Autophagy regulates satellite cell activation and myogenesis, and while elevated CO2 inhibits autophagy in inflammatory cells, it has never been evaluated in the context of hypercapnia-driven abnormal myogenesis. Using lineage tracing in pre- and post-stem cell transplantation experiments, we show that hypercapnia undermines both Pax7- and α-7 integrin-expressing satellite cells activation, replication and myogenesis. Satellite cells’ multi-omic analyses indicate that hypercapnia disrupts multiple pathways regulated by autophagy. Moreover, autophagy-specific LC3 fluorescence-reporting mouse and cellular data demonstrate that hypercapnia reduces expressions of AMPK and Ulk1, which critically participate in autophagosome formation, and has no effect on the antagonistic mTOR pathway including Ulk1 serine-757 phosphorylation. Moreover, Atg7 knockout-driven loss of autophagy function phenocopies the effects on hypercapnia. After rapamycin administration, the hypercapnia-induced myogenic deficit is corrected by a sharp AMPK activation leading to the autophagy-stimulatory Ulk1 phosphorylation at serine-555, autophagy acceleration, increased satellite cells replication and improved myogenesis post-satellite cells transplantation.
2025-01-15 | GSE266996 | GEO
Project description:Autophagosome formation requires multiple autophagy-related (ATG) factors. However, we find that a subset of autophagy substrates remains robustly targeted to the lysosome in the absence of several core ATGs, including the LC3 lipidation machinery. To address this unexpected result, we performed genome-wide CRISPR screens identifying genes required for NBR1 flux in ATG7KO cells. We find that ATG7-independent autophagy still requires canonical ATG factors including FIP200. However, in the absence of LC3 lipidation, additional factors are required including TAX1BP1 and TBK1. TAX1BP1's ability to cluster FIP200 around NBR1 cargo and induce local autophagosome formation enforces cargo specificity and replaces the requirement for lipidated LC3. In support of this model, we define a ubiquitin-independent mode of TAX1BP1 recruitment to NBR1 puncta, highlighting that TAX1BP1 recruitment and clustering, rather than ubiquitin binding per se, is critical for function. Collectively, our data provide a mechanistic basis for reports of selective autophagy in cells lacking the lipidation machinery, wherein receptor-mediated clustering of upstream autophagy factors drives continued autophagosome formation.
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Project description:The PI3K-PKB/c-akt-FOXO signalling network provides a major intracellular hub for regulation of cell proliferation, survival and stress resistance1. Here we report a novel function for FOXO transcription factors in regulating autophagy through modulation of intracellular glutamine levels. To identify novel transcriptional targets of this module we performed an unbiased microarray analysis after conditional activation of the key components PI3K, PKB, FOXO3 and FOXO4. Utilising this global pathway approach we identified glutamine synthetase (GS) as being transcriptionally regulated by PI3K-PKB-FOXO signalling. FOXO-mediated increase in GS expression specifically induced glutamine production independently of cell type, and this was evolutionary conserved. FOXO activation resulted in mTOR inhibition by preventing the translocation of mTOR to lysosomal membranes, which was dependent on GS activity. Increased GS activity resulted in increased autophagosome turnover as measured by LC3 lipidation, p62 degradation, and confocal imaging of LC3, p62, WIPI-1, ULK2 and Atg12. Inhibition of FOXO3-mediated autophagy resulted in increased apoptosis, suggesting that the induction of autophagy by FOXO3-mediated upregulation of GS is important for cellular survival. These findings reveal a novel signalling network that can directly modulate autophagy through regulation of glutamine metabolism. conditional activation of pkb and pi3k were followed in a timeseries. Each timepoint consists of 4 independent replicates, labeled with either cy3 or cy5 and put on array against time0.
2012-07-21 | E-GEOD-35701 | biostudies-arrayexpress
Project description:The PI3K-PKB/c-akt-FOXO signalling network provides a major intracellular hub for regulation of cell proliferation, survival and stress resistance1. Here we report a novel function for FOXO transcription factors in regulating autophagy through modulation of intracellular glutamine levels. To identify novel transcriptional targets of this module we performed an unbiased microarray analysis after conditional activation of the key components PI3K, PKB, FOXO3 and FOXO4. Utilising this global pathway approach we identified glutamine synthetase (GS) as being transcriptionally regulated by PI3K-PKB-FOXO signalling. FOXO-mediated increase in GS expression specifically induced glutamine production independently of cell type, and this was evolutionary conserved. FOXO activation resulted in mTOR inhibition by preventing the translocation of mTOR to lysosomal membranes, which was dependent on GS activity. Increased GS activity resulted in increased autophagosome turnover as measured by LC3 lipidation, p62 degradation, and confocal imaging of LC3, p62, WIPI-1, ULK2 and Atg12. Inhibition of FOXO3-mediated autophagy resulted in increased apoptosis, suggesting that the induction of autophagy by FOXO3-mediated upregulation of GS is important for cellular survival. These findings reveal a novel signalling network that can directly modulate autophagy through regulation of glutamine metabolism. conditional activation of foxo3 and foxo4 were followed in a timeseries. Each timepoint consists of 4 independent replicates, labeled with either cy3 or cy5 and put on array against time0 as reference.
2012-07-21 | E-GEOD-35703 | biostudies-arrayexpress