Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE70707
PROVIDER: PRJNA289591 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We utilized primary MEFs to further delineate the role of MOF in proliferating cells and demonstrate that MOF directly activates genes required for cell cycle progression.
2015-01-01 | GSE62617 | GEO
Project description:Reversible acetylation of mitochondrial proteins is a regulatory mechanism central to adaptive metabolic responses. Yet, how such functionally relevant protein acetylation is achieved remains unexplored. Here, we reveal an unprecedented role of the MYST family lysine acetyltransferase MOF in energy metabolism via mitochondrial protein acetylation. Loss of MOF-KANSL complex members led to mitochondrial defects including fragmentation, reduced cristae density and impaired mitochondrial electron transport chain (mtETC) complex IV (CIV) integrity in primary mouse embryonic fibroblasts. We demonstrate COX17, a CIV assembly factor, as a bona fide acetylation target of MOF. Loss of COX17 or expression of its non-acetylatable mutant phenocopied the mitochondrial defects observed upon MOF depletion. The acetylation-mimetic COX17 rescues these defects and maintains CIV activity even in the absence of MOF, suggesting an activatory role of mtETC protein acetylation. Fibroblasts from MOF syndrome patients with intellectual disability also revealed respiratory defects that could be restored by alternative oxidase, acetylation-mimetic COX17 or mitochondrially targeted MOF. Overall, our findings highlight the critical role of MOF-KANSL complex in mitochondrial physiology and provide new insights into MOF syndrome.
2023-10-09 | GSE199009 | GEO
Project description:Mitochondrial oxidative phosphorylation (OXPHOS) makes ATP and supports biosynthesis during proliferation, but its role in non-proliferating cells, beyond ATP production, is less understood. Here we show that OXPHOS protects quiescent (but not proliferating) cells from oxidative stress. Using in vivo models of OXPHOS deficiency (whole body and endothelium-specific) we show that OXPHOS mediated resistance to ROS (i) maintains selectivity of ROS-based anticancer therapy by protecting normal tissues during treatment, and in quiescent endothelium (ii) ameliorates systemic LPS-induced inflammation and (iii) attenuates symptoms of the inflammatory bowel disease. ROS-resistance provided by OXPHOS is independent of its role in biosynthesis or NADH recycling. Instead, in quiescent cells OXPHOS constitutively generates low levels of endogenous ROS that support basal autophagic flux and protect from exogenous ROS challenge. Hence, during evolution cells acquired mitochondria to profit from oxidative metabolism, but also built in an OXPHOS-dependent mechanism to guard against the resulting oxidative stress.
2022-10-13 | PXD021376 | Pride
Project description:We have studied the regulatory potential of MYST1-(MOF)-containing MSL and NSL complexes in mouse embryonic stem cells (ESCs) and neuronal progenitors. We find that both complexes influence transcription by binding to promoters as well as TSS-distal enhancer regions. In contrast to flies, the MSL complex is not enriched on the X chromosome yet it is crucial for mammalian X chromosome regulation as it specifically regulates Tsix ncRNA, the major repressor of Xist lncRNA. MSL depletion leads to severely decreased Tsix expression, reduced REX1 recruitment, and consequently accumulation of Xist RNA in ESCs. The NSL complex provides additional, Tsix-independent repression of Xist by maintaining pluripotency. MSL and NSL complexes therefore act synergistically by using distinct pathways to ensure a fail-safe mechanism for the repression of X inactivation in ESCs. We have performed ChIP-seq of KANSL3, MCRS1, MOF, MSL1 and MSL2 in mouse ESCs, and KANSL3, MOF and MSL2 in NPCs, in duplicate and normalised against their inputs. We have also performed RNA-seq following knockdown of Kansl3, Mof, Msl1 and Msl2 mouse embryonic stem cells in triplicate. NB: Kansl3 and Mof knockdown-RNAseq are analyzed against their own scrambled controls, and Msl1 and Msl2 against another scrambled control triplicate.
2014-06-03 | E-GEOD-57698 | biostudies-arrayexpress
Project description:Tissue-resident memory T-cells (TRM) mediate optimal protection against respiratory infections. Little is known about human TRM. Here we characterized memory T-cells from human lungs. We identify two distinct memory T-cell populations in lung tissue. Lung TRM are poised for rapid, but restrained responsiveness by constitutive expression of genes encoding effector molecules and inhibitory regulators. Although TRM express little T-bet and Eomesodermin, transcription factor signatures revealed that multiple drivers of effector gene expression are active in TRM, including Notch. We show that Notch is required for maintenance of the CD103+ TRM population in mouse lungs. These findings suggests that the lung tissue environment actively maintains the T-cells that protect it from infectious assault through activating the Notch surface receptor in TRM.
2016-10-23 | GSE79774 | GEO
Project description:Lung resident memory B cells protect against bacterial pneumonia
| PRJNA703000 | ENA
Project description:To ensure cell survival and growth during temperature increase, eukaryotic organisms respond with transcriptional activation that results in accumulation of proteins that protect against damage, and facilitate recovery. To define the global cellular adaptation response to heat stress, we performed a systematic genetic screen that yielded 277 yeast genes required for growth at high temperature. Of these, the Rpd3 histone deacetylase complex was enriched. Global gene expression analysis showed that Rpd3 partially regulated gene expression upon heat shock. The Hsf1 and Msn2/4 transcription factors are the main regulators of gene activation in response to heat stress. RPD3-deficient cells had impaired activation of Msn2/4-dependent genes, while activation of genes controlled by Hsf1 was deacetylase independent. Rpd3 bound to heat stress-dependent promoters through the Msn2/4 transcription factors, allowing entry of RNA Pol II and activation of transcription upon stress. Finally, we found that the large, but not the small Rpd3 complex regulated cell adaptation in response to heat stress.
2010-04-23 | GSE17514 | GEO
Project description:Mitochondrial oxidative phosphorylation (OXPHOS) generates ATP and is required for pyrimidine nucleotide synthesis during proliferation. In contrast, the role of OXPHOS in post-mitotic cells, beyond its contribution to ATP production, is less understood. Here, we show that in non-proliferating cells, OXPHOS ensures protection against oxidative stress by sustaining autophagy. Autophagy is suppressed and oxidative stress resistance is compromised in OXPHOS-deficient non-proliferating cells in vitro and in TFAM knockout mice in vivo, while attenuation of autophagy in OXPHOS-functional cells phenocopies the effects of OXPHOS deficiency. Mechanistically, the regulation of the autophagy / stress response by OXPHOS does not require changes in gene expression, AMPK/mTOR1/ULK1 signaling or NADH levels. Instead, OXPHOS maintains ROS levels to prevent activation of ATG4, a ROS-activated inhibitor of autophagy. We propose that protection against oxidative stress via the ROS-ATG4 axis is a novel function of mitochondrial respiration in non-proliferating cells that may have consequences for cancer therapy and beyond.
2022-01-07 | GSE146025 | GEO
Project description:To ensure cell survival and growth during temperature increase, eukaryotic organisms respond with transcriptional activation that results in accumulation of proteins that protect against damage, and facilitate recovery. To define the global cellular adaptation response to heat stress, we performed a systematic genetic screen that yielded 277 yeast genes required for growth at high temperature. Of these, the Rpd3 histone deacetylase complex was enriched. Global gene expression analysis showed that Rpd3 partially regulated gene expression upon heat shock. The Hsf1 and Msn2/4 transcription factors are the main regulators of gene activation in response to heat stress. RPD3-deficient cells had impaired activation of Msn2/4-dependent genes, while activation of genes controlled by Hsf1 was deacetylase independent. Rpd3 bound to heat stress-dependent promoters through the Msn2/4 transcription factors, allowing entry of RNA Pol II and activation of transcription upon stress. Finally, we found that the large, but not the small Rpd3 complex regulated cell adaptation in response to heat stress. Three independent 200 ml cultures of wild-type and rpd3Δ mutant strains were grown to mid-log phase in YPD rich medium at 25ºC (control) or at 39 ºC for 20 min (heat stressed). Results were analyzed comparing thermo-responsive gene expression respect to the control in each individual strain.
2010-04-23 | E-GEOD-17514 | biostudies-arrayexpress