Depletion of histone deacetylase 3 antagonizes PI3K-mediated tissue overgrowth through the acetylation of histone H4 at lysine 16
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ABSTRACT:
ORGANISM(S): Drosophila melanogaster
SUBMITTER: Wenwen Lv
PROVIDER: E-GEOD-38552 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Histone acetylation is one of the best studied gene modifications and has been shown to be involved in numerous important biological processes. Herein，we demonstrate that Hdac3 regulates both organ and body size through the deacetylation of histone H4 at lysine 16 (H4K16ac). H4K16ac is affected by PI3K signaling cascades. Increasing H4K16ac by the depletion of Hdac3 counteracts PI3K-induced tissue overgrowth and PI3K-mediated alterations in the transcription profile. Using microarry, we compared the transcriptional profile between flies over-expressing PI3K and flies co-expressing PI3K and Hdac3 dsRNA. The findings provide further insight into the mechanism of PI3K-mediated growth and chromatin remodeling.
2012-06-20 | GSE38552 | GEO
Project description:We address the function of HEXIM, an inhibitor of the general transcriptional elongation regulator P-TEFb which regulates the transcriptional status of many developmental genes, during Drosophila development. We showed that HEXIM knockdown mutants display organs development failure. In the wing disc, it induces apoptosis and affects Hh signaling. The continuous death of proliferative cells is compensated by apoptosis-induced cell proliferation, in a manner similar to that of differentiated cells, together with high levels of Hh and Ci. We completed this analysis with microarrays to characterize the molecular phenotype of HEXIM knockdown during eye differentiation. HEXIM knockdown during eye differentiation was carried out with a UAS-Hexim-RNAi strain crossed with a GMR-Gal4 driver strain (Bloomington stock center)). Adult GMR>RNAi Hexim flies display slightly smaller, rough and often necrosed eyes. Total RNA were collected from isolated heads. We then used microarray to compare the transcriptome of HEXIM knockdown mutant with that of wild type flies.
2014-07-31 | E-GEOD-54590 | biostudies-arrayexpress
Project description:The goal of this gene expression profiling experiment was to identify the entire set of transcription factors expressed during late pupal wing development (~80h APF) when pigmentation genes are expressed We used Affymetrix microarrays to profile the expression of the transcription factors in late pupal wings of Oregon R flies. The staging of the flies was made by eye, based on the extent of wing pigmentation. RNA was extracted from batches of 40 flies and three biological replicates were analyzed.
2013-02-01 | E-GEOD-43673 | biostudies-arrayexpress
Project description:Insect development requires genes to be expressed in strict spatiotemporal order. The degree of histone acetylation regulates insect development, via histone acetyltransferases (HATs) and histone deacetylases (HDACs). Although HDAC3 is required for early embryonic development, its functions in Helicoverpa armigera remain unclear. We treated H. armigera with HDAC3 siRNA and RGFP966, a specific inhibitor, examining how HDAC3 loss-of-function affects growth and development. HDAC3 siRNA and RGFP966 treatment increased mortality at each growth-stage and altered metamorphosis, hampering pupation and causing abnormal wing development, reduced egg production, and reduced hatching rate. RNA-seq analysis identified 2,788 differentially expressed genes (≥ two-fold change; P ≤ 0.05) between siHDAC3- and siNC-treated larvae. Kr-h1, were differentially expressed in HDAC3 knockdown larvae. Pathway enrichment analysis revealed significant enrichment of genes involved in the Hippo, MAPK, and Wnt signaling pathways following HDAC3 knockdown. Histone H3K9 acetylation was increased in H. armigera after siHDAC3 treatment. In conclusion, HDAC3-knockdown dysregulated 20-hydroxyecdysone hormone-related and apoptosis-related genes in H. armigera, affecting many basic processes, including cell cycle regulation, metabolism, and signal transduction. The Result showed that HDAC3 gene can serve as a potential target for fighting against Helicoverpa armigera.
2022-12-14 | GSE215090 | GEO
Project description:Epigenetic regulation by histone acetylation plays a key role in cellular homeostasis and its misregulation is associated with human disease. Histone 4 Lysine 16 acetylation (H4K16ac) serves a unique role amongst the many histone modifications as it directly affects chromatin structure1. The Male Specific Lethal (MSL) complex associated MOF/KAT8 histone acetyl transferase is responsible for bulk H4K16ac in flies and mammals. Yet, its importance during human development and a potential involvement in human pathologies remains largely unknown. Here, we uncover that pathogenic variants in MSL3, a component of the MSL complex, are causative for a new recognizable X-linked syndrome affecting Histone 4 Lysine 16 acetylation (H4K16ac) in both male and female individuals. Common clinical features of the syndrome include global developmental delay comprising profound speech delay, delayed ability to walk and craniofacial dysmorphism. Using patient-derived primary fibroblasts, we demonstrate that de novo variants or deletions of MSL3 affect the assembly and enzymatic activity of the MSL complex, hence impacting on global H4K16ac levels. Transcriptome analysis from patient cells showed misregulation of cellular pathways involved in serotonergic signaling, morphogenesis, axon guidance and cell structure. Finally, using HDAC inhibitor treatment, we can rescue expression of downregulated target genes, offering potential therapeutic avenues for MSL3-mutated patients. Taken together, we characterize a novel syndrome, named ILyADe (Impaired Lysine 16 acetylation associated disorder), which is caused by mutations of an epigenetic regulator, allowing us for the first time to unravel the crucial role of H4K16ac during human development. ILyaDe thus constitutes a new class of syndromes associated with misregulation of a single epigenetic modification caused by a genetic alteration.
2018-09-18 | PXD009317 | Pride
Project description:In order to analyze the global changes in gene expression resulting from induction of NetA-Fra signaling, we carried out a microarray experiment comparing Drosophila third instar wing imaginal discs in which Net+Fra had been overexpressed to age matched wild type wing imaginal discs. RNA extracted from both +NetA-Fra overexpression and wildtype third instar imaginal discs were hybridized to the Affymetrix GeneChip Drosophila Genome 2.0 . Heat shock induced GFP-marked clones ectopically expressing NetA+Fra in larvae were generated. Controls for this study included age matched wildtype third instar wing imaginal discs bearing GFP clones which were prepared in the same manner. Total RNA was extracted from dissected +NetA-Fra vs. control third instar wing imaginal discs and hybridized to the Affymetrix GeneChip Drosophila Genome 2.0.
2013-05-21 | E-GEOD-47113 | biostudies-arrayexpress
Project description:RNA-seq was performed to confirm the effect of dMyc overexpression or RNAi repression on conserved Myc targets in the Drosophila wing disc.
2022-04-26 | E-MTAB-9328 | biostudies-arrayexpress
Project description:The Drosophila gene dLmo encodes a transcriptional regulator involved in wing development and behavioral responses to cocaine and ethanol. We were interested in discovering novel transcriptional targets of dLmo in the nervous system by examining gene expression changes in the heads of wild-type flies and flies carrying dLmo loss-of-function (EP1306) and gain-of-function mutants (BxJ). RNA was isolated from 3 pooled groups of 200 fly heads from each genotype (w;iso control, EP1306, and BxJ) and hybridized to triplicate Affymetrix Drosophila 2.0 oligonucleotide microarray chips at the Partners HealthCare Center for Personalized Genetic Medicine microarray facility (Harvard University).
2011-02-01 | E-GEOD-25988 | biostudies-arrayexpress
Project description:Before zygotic genome activation (ZGA) the quiescent genome undergoes reprogramming to transition into the transcriptionally active state. However, the mechanisms underlying euchromatin establishment during early embryogenesis remain poorly understood. Here, we show that histone H4 lysine-16 acetylation (H4K16ac) is maintained from oocytes to fertilized embryos in Drosophila and mammals. H4K16ac forms large domains that control nucleosome accessibility of promoters prior to ZGA in flies. Maternal depletion of MOF acetyl-transferase leading to H4K16ac loss causes aberrant Pol II recruitment, compromises the 3D organization of the active genomic compartments during ZGA and consequently causes downregulation of post-zygotically expressed genes. Germline depletion of histone deacetylases revealed that other acetyl marks cannot compensate for H4K16ac loss in the oocyte. Moreover, zygotic re-expression of MOF was neither able to restore embryonic viability nor onset of X chromosome dosage compensation. Thus, maternal H4K16ac provides an instructive function to the offspring, priming future gene activation.
2020-06-04 | GSE130335 | GEO
Project description:Epigenetic regulation by histone acetylation plays a key role in cellular homeostasis and its misregulation is associated with human disease. The Male Specific Lethal (MSL) complex associated MOF/KAT8 histone acetyl-transferase is responsible for bulk Histone 4 Lysine 16 acetylation (H4K16ac) in flies and mammals. H4K16ac is a peculiar case amongst the many histone tail modifications in directly affecting higher order chromatin compaction. Yet, its importance during human development and a potential involvement in human pathologies remains largely unknown. Here, we uncover that pathogenic variants in MSL3, a component of the MSL complex, are causative for a new recognizable X-linked syndrome affecting both male and female individuals. Common clinical features of the syndrome include a global delay in developmental milestones and speech, a progressive gait disturbance and recognizable dysmorphism. Using skin biopsies and patient-derived primary fibroblasts, we demonstrate that de novo variants or deletions of MSL3 affect the assembly and enzymatic activity of the MSL complex, hence globally impacting H4K16ac levels in vivo. Transcriptome analysis from patient cells showed misregulation of cellular pathways involved in morphogenesis, cellular shape and cell migration. Using RNAi and MSL3 reintroduction experiments, we phenocopy acute responses occurring on H4K16ac-sensitive MSL target genes, supporting that this syndrome is caused by the loss of MSL3. Finally, we use HDAC inhibitors to rebalance acetylation levels and are able to alleviate both molecular and cellular phenotypes of MSL3 patients cells. Taken together, we characterize a novel syndrome, which is caused by mutations of an epigenetic regulator, allowing us for the first time to unravel the crucial role of H4K16ac during human development.
2018-08-06 | GSE102250 | GEO