Similar Datasets
Project description:Quantitative acetylomics reveals substrates of lysine acetyltransferase GCN5 in adult and aging Drosophila
| PRJNA913122 | ENA
Project description:Acetylome and proteome of WT (5905), gcn5 loss-of-function, and GCN5 overexpression Drosophila at age of 3d Acetylome and proteome of WT (5905) Drosophila during aging (at age of 3d, 15d, 30d, and 45d)
2022-12-22 | PXD039046 |
Project description:Parasitic protozoa such as the apicomplexan Toxoplasma gondii progress through their life cycle in response to stimuli in the environment or host organism. Very little is known about how proliferating tachyzoites reprogram their expressed genome in response to stresses that prompt development into latent bradyzoite cysts. We have previously linked histone acetylation with the expression of stage-specific genes, but the factors involved remain to be determined. We sought to determine if GCN5, which operates as a transcriptional co-activator by virtue of its histone acetyltransferase (HAT) activity, contributed to stress-induced changes in gene expression in Toxoplasma. In contrast to other lower eukaryotes, Toxoplasma has duplicated its GCN5 lysine acetyltransferase (KAT). Disruption of the gene encoding for TgGCN5-A did not produce a severe phenotype under normal culture conditions, but here we show that the TgGCN5-A null mutant is deficient in recovering from alkaline pH, a common stress used to induce bradyzoite differentiation in vitro. The TgGCN5-A knockout is incapable of up-regulating key marker genes expressed during development of the latent cyst form. Complementation of the TgGCN5-A knockout restores the expression of these stress-induced genes and reverses the stress recovery defect. We also describe a genome-wide analysis of the Toxoplasma transcriptional response to alkaline pH stress, finding that TgGCN5-A knockout parasites fail to up-regulate 68% of the stress response genes that are induced 2-fold or more in wild-type. Using chromatin immunoprecipitation, we verify an enrichment of TgGCN5-A at the upstream regions of genes activated by alkaline pH exposure, including developmentally regulated genes. Wild-type and GCN5-A- Knockout organisms were subjected to control and stress treatments
2011-05-25 | E-GEOD-22100 | biostudies-arrayexpress
Project description:80% of the genomic binding sites of the histone acetyltransferase Gcn5 are colocalizing with CP190 binding. Depletion of CP190 reduces the number of Gcn5 binding sites and binding strength to chromatin. Binding dependency was further supported by Gcn5 mediated co-precipitation of CP190
2016-12-05 | GSE83408 | GEO
Project description:80% of the genomic binding sites of the histone acetyltransferase Gcn5 are colocalizing with CP190 binding. Depletion of CP190 reduces the number of Gcn5 binding sites and binding strength to chromatin. Binding dependency was further supported by Gcn5 mediated co-precipitation of CP190
2016-12-05 | GSE83406 | GEO
Project description:Parasitic protozoa such as the apicomplexan Toxoplasma gondii progress through their life cycle in response to stimuli in the environment or host organism. Very little is known about how proliferating tachyzoites reprogram their expressed genome in response to stresses that prompt development into latent bradyzoite cysts. We have previously linked histone acetylation with the expression of stage-specific genes, but the factors involved remain to be determined. We sought to determine if GCN5, which operates as a transcriptional co-activator by virtue of its histone acetyltransferase (HAT) activity, contributed to stress-induced changes in gene expression in Toxoplasma. In contrast to other lower eukaryotes, Toxoplasma has duplicated its GCN5 lysine acetyltransferase (KAT). Disruption of the gene encoding for TgGCN5-A did not produce a severe phenotype under normal culture conditions, but here we show that the TgGCN5-A null mutant is deficient in recovering from alkaline pH, a common stress used to induce bradyzoite differentiation in vitro. The TgGCN5-A knockout is incapable of up-regulating key marker genes expressed during development of the latent cyst form. Complementation of the TgGCN5-A knockout restores the expression of these stress-induced genes and reverses the stress recovery defect. We also describe a genome-wide analysis of the Toxoplasma transcriptional response to alkaline pH stress, finding that TgGCN5-A knockout parasites fail to up-regulate 68% of the stress response genes that are induced 2-fold or more in wild-type. Using chromatin immunoprecipitation, we verify an enrichment of TgGCN5-A at the upstream regions of genes activated by alkaline pH exposure, including developmentally regulated genes.
2011-05-25 | GSE22100 | GEO
Project description:rs05-09_histone-acetylase - gcn5 - Different genes show an opposed expression profile in gcn5 compared to hd1. For these genes, the double mutant might show an expression similar to the wild type. - gcn5, hd1 or double mutant gcn5hd1 were grown on MS during 10 days (1.03 boyes stage). Keywords: gene knock out 3 dye-swaps - CATMA arrays
2009-04-10 | E-GEOD-15560 | biostudies-arrayexpress
Project description:The development of CD1d-restricted invariant natural killer T (iNKT) cells, a population that is critical for both innate and adaptive immunity, is regulated by multiple transcription factors, but the molecular mechanisms underlying how the transcriptional activation of these factors are regulated during iNKT development remain largely unknown. We found that the histone acetyltransferase general control non-derepressible 5 (GCN5) is essential for iNKT cell development during the maturation stage. GCN5 deficiency blocked iNKT cell development in a cell-intrinsic manner. At the molecular level, GCN5 is a specific lysine acetyltransferase of early growth responsive gene 2 (EGR2), a transcription factor required for iNKT cell development. GCN5-mediated acetylation positively regulated EGR2 transcriptional activity, and both genetic and pharmacological GCN5 suppression specifically inhibited the transcription of EGR2 target genes in iNKT cells, including Runx1, promyelocytic leukemia zinc finger protein (PLZF), interleukin (IL)-2Rb, and T-bet. Therefore, our study revealed GCN5-mediated EGR2 acetylation as a molecular mechanism that regulates iNKT development.
| S-EPMC5772774 | biostudies-other
Project description:rs05-09_histone-acetylase - gcn5 - Different genes show an opposed expression profile in gcn5 compared to hd1. For these genes, the double mutant might show an expression similar to the wild type. - gcn5, hd1 or double mutant gcn5hd1 were grown on MS during 10 days (1.03 boyes stage). Keywords: gene knock out
2009-04-11 | GSE15560 | GEO
Project description:Lysine acetylation is a critical posttranslational modification that influences protein activity, stability, and binding properties. The acetylation of histone proteins in particular is a well-characterized feature of gene expression regulation. In the protozoan parasiteToxoplasma gondii, a number of lysine acetyltransferases (KATs) contribute to gene expression and are essential for parasite viability. The natural product garcinol was recently reported to inhibit enzymatic activities of GCN5 and p300 family KATs in other species. Here we show that garcinol inhibits TgGCN5b, the only nuclear GCN5 family KAT known to be required forToxoplasmatachyzoite replication. Treatment of tachyzoites with garcinol led to a reduction of global lysine acetylation, particularly on histone H3 and TgGCN5b itself. We also performed transcriptome sequencing (RNA-seq), which revealed increasing aberrant gene expression coincident with increasing concentrations of garcinol. The majority of the genes that were most significantly affected by garcinol were also associated with TgGCN5b in a previously reported chromatin immunoprecipitation assay with microarray technology (ChIP-chip) analysis. The dysregulated gene expression induced by garcinol significantly inhibitsToxoplasmatachyzoite replication, and the concentrations used exhibit no overt toxicity on human host cells. Garcinol also inhibitsPlasmodium falciparumasexual replication with a 50% inhibitory concentration (IC50) similar to that forToxoplasma Together, these data support that pharmacological inhibition of TgGCN5b leads to a catastrophic failure in gene expression control that prevents parasite replication.
| S-EPMC4808158 | biostudies-literature