Long Noncoding RNA TINCR-mediated Regulation of Acetyl-CoA Metabolism Promotes Nasopharyngeal Carcinoma Progression and Chemoresistance
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA574071 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10182175_1.fastq.gz | Fastqsanger.gz | |||
| SRR10182175_2.fastq.gz | Fastqsanger.gz | |||
| SRR10182176_1.fastq.gz | Fastqsanger.gz | |||
| SRR10182176_2.fastq.gz | Fastqsanger.gz | |||
| SRR10182177_1.fastq.gz | Fastqsanger.gz |
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Project description:Our present study showed that lncRNA TINCR have impact on the ubiquitination-mediated degradation level of ACLY protein in nasopharyngeal carcinoma. Silencing of TINCR lead to downregulation of ACLY protein level. ACLY is a cytosolic homotetrameric enzyme catalyzing the ATP-dependent conversion of citrate and coenzyme A (CoA) to oxaloacetate and acetyl-CoA, a precursor for lipid biosynthesis, including cholesterol, free fatty acid and phospholipid. Meanwhile, the cellular acetyl-CoA pool is also required for acetylation reactions that modify proteins such as histone acetylation, including Histone H3 acetylation K27 (H3K27ac). To select the shared genes that were regulated by TINCR and were in response to acetyl-CoA alteration, we conducted RNA-seq in HONE-1 cells with or without TINCR or ACLY silencing, as well as H3K27ac Chromatin Immunoprecipitation sequencing (ChIP-seq) in HONE-1 cells with or without ACLY silencing. We also performed CLIP-seq in HONE-1 and SUNE-1 cells to validate the TINCR-ACLY interaction and identify the binding sites of TINCR with ACLY.
2022-09-25 | GSE137977 | GEO
Project description:Cytosolic acetyl-coenzyme A is a precursor for many biotechnologically relevant compounds produced by Saccharomyces cerevisiae. In this yeast, cytosolic acetyl-CoA synthesis and growth strictly depend on expression of either the Acs1 or Acs2 isoenzyme of acetyl-CoA synthetase (ACS). Since hydrolysis of ATP to AMP and pyrophosphate in the ACS reaction constrains maximum yields of acetyl-CoA-derived products, this study explores replacement of ACS by two ATP-independent pathways for acetyl-CoA synthesis. After evaluating expression of different bacterial genes encoding acetylating acetaldehyde dehydrogenase (A-ALD) and pyruvate-formate lyase (PFL), acs1M-NM-^T acs2M-NM-^T S. cerevisiae strains were constructed in which A-ALD or PFL successfully replaced ACS. In A-ALD-dependent strains, aerobic growth rates of up to 0.27 h-1 were observed, while anaerobic growth rates of PFL-dependent S. cerevisiae (0.21 h-1) were stoichiometrically coupled to formate production. In glucose-limited chemostat cultures, intracellular metabolite analysis did not reveal major differences between A-ALD-dependent and reference strains. However, biomass yields on glucose of A-ALD- and PFL-dependent strains were lower than those of the reference strain. Transcriptome analysis suggested that reduced biomass yields were caused by acetaldehyde and formate in A-ALD- and PFL-dependent strains, respectively. Transcript profiles also indicated that a previously proposed role of Acs2 in histone acetylation is probably linked to cytosolic acetyl-CoA levels rather than to direct involvement of Acs2 in histone acetylation. While, for the first time, demonstrating that yeast ACS can be fully replaced by alternative reactions, this study demonstrates that further modifications are needed to achieve optimal in vivo efficiencies of the supply of acetyl-CoA as product precursor. To investigate the impact of introduced changes in native pathway of cytosolic acetyl-CoA formation in S. cerevisiae, a DNA microarray-based transcriptome analysis was performed on aerobic or anaerobic, glucose-limited chemostat cultures.
2013-11-21 | E-GEOD-47983 | biostudies-arrayexpress
Project description:Cytosolic acetyl-coenzyme A is a precursor for many biotechnologically relevant compounds produced by Saccharomyces cerevisiae. In this yeast, cytosolic acetyl-CoA synthesis and growth strictly depend on expression of either the Acs1 or Acs2 isoenzyme of acetyl-CoA synthetase (ACS). Since hydrolysis of ATP to AMP and pyrophosphate in the ACS reaction constrains maximum yields of acetyl-CoA-derived products, this study explores replacement of ACS by two ATP-independent pathways for acetyl-CoA synthesis. After evaluating expression of different bacterial genes encoding acetylating acetaldehyde dehydrogenase (A-ALD) and pyruvate-formate lyase (PFL), acs1Δ acs2Δ S. cerevisiae strains were constructed in which A-ALD or PFL successfully replaced ACS. In A-ALD-dependent strains, aerobic growth rates of up to 0.27 h-1 were observed, while anaerobic growth rates of PFL-dependent S. cerevisiae (0.21 h-1) were stoichiometrically coupled to formate production. In glucose-limited chemostat cultures, intracellular metabolite analysis did not reveal major differences between A-ALD-dependent and reference strains. However, biomass yields on glucose of A-ALD- and PFL-dependent strains were lower than those of the reference strain. Transcriptome analysis suggested that reduced biomass yields were caused by acetaldehyde and formate in A-ALD- and PFL-dependent strains, respectively. Transcript profiles also indicated that a previously proposed role of Acs2 in histone acetylation is probably linked to cytosolic acetyl-CoA levels rather than to direct involvement of Acs2 in histone acetylation. While, for the first time, demonstrating that yeast ACS can be fully replaced by alternative reactions, this study demonstrates that further modifications are needed to achieve optimal in vivo efficiencies of the supply of acetyl-CoA as product precursor.
2013-11-21 | GSE47983 | GEO
Project description:Acetyl-Coenzyme A (acetyl-CoA) is a central metabolite and the acetyl source for protein acetylation, particularly histone acetylation that promotes gene expression. However, the effect of acetyl-CoA levels on histone acetylation status in plants remains unknown. Here, we show that malfunctioned cytosolic acetyl-CoA carboxylase1 (ACC1) in Arabidopsis leads to elevated levels of acetyl-CoA and promotes histone hyperacetylation predominantly at lysine 27 of histone H3 (H3K27). The increase of H3K27 acetylation (H3K27ac) is dependent on ATP-citrate lyase which cleaves citrate to acetyl-CoA in the cytoplasm, and requires histone acetyltransferase GCN5. A comprehensive analysis of the transcriptome and metabolome in combination with the genome-wide H3K27ac profiles of acc1 mutants, demonstrate the dynamic changes of H3K27ac, gene transcripts and metabolites occurring in the cell by the increased levels of acetyl-CoA. This study suggests that H3K27ac is an important link between cytosolic acetyl-CoA level and gene expression in response to the dynamic metabolic environments in plants.
2017-09-25 | GSE79524 | GEO
Project description:In order to identify regions of the genome that display quantitative changes in acetyl-CoA, we utilized an established “spike-in” normalization method that allows the quantitative comparison of histone modifications across cell populations using defined quantities of a reference epigenome. We found that some regions of the genome are more sensitive to changes in acetyl-CoA compared to others.
2018-12-20 | GSE109340 | GEO
Project description:Metabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and directchum regulator of histone acetylation in neurons and of long-term mammalian memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory. These results reveal a unique connection between cellular metabolism and neural plasticity, and establish a link between generation of acetyl-CoA and neuronal chromatin regulation. Genome-wide examination of histone H3 and H4 acetylation, as well as ACSS2 binding, in undifferentiated CAD cells and differentiated CAD neurons; background adjusted by H3 ChIP or Input.
2017-05-01 | E-GEOD-76850 | biostudies-arrayexpress
Project description:Metabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and direct regulator of histone acetylation in neurons and of long-term mammalian memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory. These results reveal a unique connection between cellular metabolism and neural plasticity, and establish a link between generation of acetyl-CoA and neuronal chromatin regulation. Global survey of gene expression in CAD cells and differentiated CAD neurons following lentiviral knockdown of ACSS2 or ATP citrate lyase (ACL) (and control = scramble hairpin); survey of hippocampal gene expression changes associated with retrieval of fear memory, after ACSS2-AAV knockdown or in EGFP-AAV control (comparison of 0h vs. 1h post-memory retrieval).
2017-05-01 | E-GEOD-76853 | biostudies-arrayexpress
Project description:Genome wide identification of acetyl-CoA regulated loci
| PRJNA430511 | ENA
Project description:Liver tumors had high levels of histone acetylation. Nrf2 knockout mice developed fewer tumors than Nrf2 wild-type mice. The mechanistic study found that Nrf2 knockout reduced the generation of acetyl CoA from impaired glycolysis, TCA cycle, and fatty acid metabolism. Acetyl CoA is the substrate for protein acetylation including histone acetylation. Here we determined the genome-wide distribution of AcH3K27. We found that Nrf2 through regulating acetyl CoA production affects histone acetylation (AcH3K27) to modulate the expression of genes, whose products were involved in the glycolysis, TCA cycle, fatty acid metabolism, and oncogenic Myc/mTor signaling. Our findings supported an Nrf2-integrated metabolic, epigenetic and oncogenic signaling in driving liver tumor development.
2023-03-20 | GSE227068 | GEO
Project description:The acetyl-CoA transporter, AT-1 (also referred to as SLC33A1), is a key member of the endoplasmic reticulum (ER) acetylation machinery; it transports acetyl-CoA from the cytosol into the ER lumen where it serves as donor of the acetyl group for Nε-lysine acetylation 1,2. Dysfunctional ER acetylation, as caused by heterozygous or homozygous mutations as well as gene duplication events of AT-1/SLC33A1, has been linked to both developmental and age-associated human diseases 3-7. Mice with reduced or increased AT-1 expression mimic associated human diseases 8-10. In this study, we investigated the pervasive effects that dysregulated AT-1 has on intracellular acetyl-CoA homeostasis. Specifically, we used AT-1S113R/+ mice 8, a model of AT-1 haploinsufficiency, and AT-1 sTg mice 10, a model of AT-1 overexpression. We found that reduced AT-1 activity in AT-1S113R/+ mice led to increased availability of acetyl-CoA in the cytosol and spontaneous steatosis. Conversely, increased AT-1 activity decreased the availability of acetyl-CoA in the cytosol and made the animals resistant to diet-induced steatosis. Both models displayed significant metabolic adaptation involving different cellular organelles and compartments. Mechanistically, the metabolic adaptation was driven by changes in both protein levels (proteome) and stoichiometry of acetylation (acetylome) within fundamental pathways. Collectively, our results suggest that AT-1 acts as an important metabolic regulator that maintains acetyl-CoA homeostasis by promoting functional “cross-talk” between different intracellular organelles and compartments.
2019-08-05 | PXD013736 | Pride