Role of yeast Nup60 lysine 467 acetylation in regulation of transcription
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ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE199740 | GEO | 2022/06/16
REPOSITORIES: GEO
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Project description:Although protein acetylation is widely observed, it has been associated with few specific regulatory functions making it poorly understood. To interrogate its functionality, we analyzed the acetylome in Escherichia coli knockout mutants of cobB, the only known sirtuin-like deacetylase, and patZ, the best-known protein acetyltransferase. For four growth conditions, more than 2,000 unique acetylated peptides, belonging to 809 proteins, were identified and differentially quantified. Nearly 65% of these proteins are related to metabolism. The global activity of CobB contributes to the deacetylation of a large number of substrates and has a major impact on physiology. Apart from the regulation of acetyl-CoA synthetase, we found that CobB-controlled acetylation of isocitrate lyase contributes to the fine-tuning of the glyoxylate shunt. Acetylation of the transcription factor RcsB prevents DNA binding, activating flagella biosynthesis and motility, and increases acid stress susceptibility. Surprisingly, deletion of patZ increased acetylation in acetate cultures, which suggests that it regulates the levels of acetylating agents. The results presented offer new insights into functional roles of protein acetylation in metabolic fitness and global cell regulation. In this study we aimed to discover how the deregulation of protein acetylation could alter physiology in E. coli. We observed that the deletion of both cobB or patZ genes in E. coli altered gene expression, specially those genes related with motility, chemotaxis and acid stress response. We used three biological replicates in this study and each condition. The control in these experiments was E. coli BW25113
2014-10-07 | E-GEOD-62094 | biostudies-arrayexpress
Project description:Role of yeast Nup60 lysine 467 acetylation in regulation of transcription
| PRJNA821419 | ENA
Project description:Although protein acetylation is widely observed, it has been associated with few specific regulatory functions making it poorly understood. To interrogate its functionality, we analyzed the acetylome in Escherichia coli knockout mutants of cobB, the only known sirtuin-like deacetylase, and patZ, the best-known protein acetyltransferase. For four growth conditions, more than 2,000 unique acetylated peptides, belonging to 809 proteins, were identified and differentially quantified. Nearly 65% of these proteins are related to metabolism. The global activity of CobB contributes to the deacetylation of a large number of substrates and has a major impact on physiology. Apart from the regulation of acetyl-CoA synthetase, we found that CobB-controlled acetylation of isocitrate lyase contributes to the fine-tuning of the glyoxylate shunt. Acetylation of the transcription factor RcsB prevents DNA binding, activating flagella biosynthesis and motility, and increases acid stress susceptibility. Surprisingly, deletion of patZ increased acetylation in acetate cultures, which suggests that it regulates the levels of acetylating agents. The results presented offer new insights into functional roles of protein acetylation in metabolic fitness and global cell regulation. In this study we aimed to discover how the deregulation of protein acetylation could alter physiology in E. coli. We observed that the deletion of both cobB or patZ genes in E. coli altered gene expression, specially those genes related with motility, chemotaxis and acid stress response.
2014-10-07 | GSE62094 | GEO
Project description:Acetyl-CoA participates in post-translational modification of proteins, central carbon and lipid metabolism in several cell compartments. In mammals, the acetyl-CoA transporter 1 (AT1) facilitates the flux of cytosolic acetyl-CoA into the endoplasmic reticulum (ER), enabling the acetylation of proteins of the secretory pathway, in concert with dedicated acetyltransferases including Nat8. However, the implication of the ER acetyl-CoA pool in acetylation of ER-transiting proteins and their relevance throughout the parasites’ life cycle is unknown. Here, we evaluated the impact of blocking putative cytosolic acetyl-CoA import on acetylation of proteins through KO of the homologue of AT1 in the parasite Toxoplasma gondii.
2022-07-25 | PXD030932 | Pride
Project description:Creating long-lasting memories relies on learning-induced changes in gene expression, which are regulated by epigenetic modifications of DNA and associated histone proteins. Post-translational modifications (PTMs) of histone proteins are key regulators of transcription, with different PTMs producing unique effects on gene activity and behavior. Although recent studies began to investigate histone variants as key regulators of memory formation, PTMs are rarely considered in relation to their function. Here, we analyze the role of acetylation of histone variant H2A.Z.1 in memory and gene expression. To this end, we developed AAV constructs to overexpress mutated H2A.Z.1 isoforms that either mimic acetylation (acetyl-mimetic) by replacing lysines 4, 7 and 11 with glutamine (KQ), or that have impaired acetylation (acetyl-defective) by replacing the same lysine with alanine (KA). We found that overexpression of the acetyl-mimetic (H2A.Z.1KQ) or the acetyl-defective (H2A.Z.1KA) isoforms of H2A.Z.1 in the hippocampus produces different effects on memory depending on strength of the task and sex, with H2A.Z.1KQ generally having a beneficial effect on memory, while H2A.Z.1KA results in impaired memory. We further analyzed gene expression data and found that H2A.Z.1KQ and H2A.Z.1KA uniquely impact the expression of different classes of genes in females and males. However, different genes are regulated by different isoforms in the 2 sexes. Finally, we describe, for the first time, that H2A.Z is involved in the alternative splicing of neuronal genes. Notably, H2A.Z depletion and its replacement with different isoforms influence transcription and splicing of different genes, suggesting that H2A.Z.1 can regulate genes through splicing and expression levels. This is the first study demonstrating that direct manipulation of the levels of AcH2A.Z regulates memory, gene expression and splicing. Overall, this study adds another layer of complexity to the contribution of histone variants to higher brain functions, consolidating H2A.Z as a key regulator of memory.
2024-03-01 | GSE242179 | 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:Creating long-lasting memories relies on learning-induced changes in gene expression, which are regulated by epigenetic modifications of DNA and associated histone proteins. Post-translational modifications (PTMs) of histone proteins are key regulators of transcription, with different PTMs producing unique effects on gene activity and behavior. Although recent studies began to investigate histone variants as key regulators of memory formation, PTMs are rarely considered in relation to their function. Here, we analyze the role of acetylation of histone variant H2A.Z.1 in memory and gene expression. To this end, we developed AAV constructs to overexpress mutated H2A.Z.1 isoforms that either mimic acetylation (acetyl-mimetic) by replacing lysines 4, 7 and 11 with glutamine (KQ), or that have impaired acetylation (acetyl-defective) by replacing the same lysine with alanine (KA). We found that overexpression of the acetyl-mimetic (H2A.Z.1KQ) or the acetyl-defective (H2A.Z.1KA) isoforms of H2A.Z.1 in the hippocampus produces different effects on memory depending on strength of the task and sex, with H2A.Z.1KQ generally having a beneficial effect on memory, while H2A.Z.1KA results in impaired memory. We further analyzed gene expression data and found that H2A.Z.1KQ and H2A.Z.1KA uniquely impact the expression of different classes of genes in females and males. However, different genes are regulated by different isoforms in the 2 sexes. Finally, we describe, for the first time, that H2A.Z is involved in the alternative splicing of neuronal genes. Notably, H2A.Z depletion and its replacement with different isoforms influence transcription and splicing of different genes, suggesting that H2A.Z.1 can regulate genes through splicing and expression levels. This is the first study demonstrating that direct manipulation of the levels of AcH2A.Z regulates memory, gene expression and splicing. Overall, this study adds another layer of complexity to the contribution of histone variants to higher brain functions, consolidating H2A.Z as a key regulator of memory.
2024-03-05 | GSE260704 | GEO
Project description:In this study, we set out to clarify the role of lysine acetylation on the major yeast Hsp40, Ydj1. We mutated a series of acetylation sites on Ydj1s J domain to either arginine to block acetylation or glutamine to mimic constitutive acetylation.
2024-04-14 | MSV000094536 | MassIVE
Project description:Oxidative stress adaptation strategies are important to cell function and are linked to cardiac, neurodegenerative disease and cancer. Representatives of the domain Archaea are used as model organisms based on their extreme tolerance to oxidants and close evolutionary relationship with eukaryotes. Study of the halophilic archaeon Haloferax volcanii reveals lysine acetylation to be associated with oxidative stress responses. The strong oxidant hypochlorite: i) stimulates an increase in lysine acetyltransferase HvPat2 to HvPat1 abundance ratios and ii) selects for lysine deacetylase sir2 mutants. Here we report the dynamic occupancy of the lysine acetylome of glycerol-grown H. volcanii as it shifts in profile in response to hypochlorite. These findings are revealed by the: 1) quantitative multiplex LC-MS/MS analysis of the SILAC-compatible parent and Δsir2 mutant strains and 2) label free LC-MS/MS analysis of H26 ‘wild type’ cells. The results show that lysine acetylation is associated with key biological processes including DNA topology, central metabolism, cobalamin biosynthesis and translation. Lysine acetylation targets are found conserved across species. Moreover, lysine residues modified by acetylation and ubiquitin-like sampylation are identified suggesting post-translational modification (PTM) crosstalk. Overall, the results of this study expand the current knowledge of lysine acetylation in Archaea, with the long-term goal to provide a balanced evolutionary perspective of PTM systems in living organisms.
2023-07-20 | PXD041799 | Pride
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