KDM5 occupancy and expression profiling of kdm5 mutant flies and wt flies under normal condition and oxidative stress
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA289117PRJNA289118
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE70591 | GEO | 2015/12/22
SECONDARY ACCESSION(S): PRJNA289116
REPOSITORIES: GEO
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Project description:Comparing the transcriptome of wildtype and kdm5 mutant flies in normal conditions revealed a total of 4787 genes that were significantly downregulated and thus require KDM5 for their activation, and 3269 upregulated genes that are normally repressed by KDM5 (p<0.05, FDR <0.05). Because kdm5 mutants are sensitive to the oxidizer paraquat, we also carried out RNA-seq from wildtype and kdm5 mutant adults in oxidative stress conditions. Paraquat treatment of wildtype flies lead to the upregulation of 2481, and downregulation of 3103 genes
2015-12-22 | GSE70590 | GEO
Project description:Comparing the transcriptome of wildtype and kdm5 mutant flies in normal conditions revealed a total of 4787 genes that were significantly downregulated and thus require KDM5 for their activation, and 3269 upregulated genes that are normally repressed by KDM5 (p<0.05, FDR <0.05). Because kdm5 mutants are sensitive to the oxidizer paraquat, we also carried out RNA-seq from wildtype and kdm5 mutant adults in oxidative stress conditions. Paraquat treatment of wildtype flies lead to the upregulation of 2481, and downregulation of 3103 genes adult mRNA profiles of 1-3-days old wild type (WT) and kdm5 mutant under normal condition and oxitative stress were generated by deep sequencing, using Illumina HisSeq 2000.
2015-12-22 | E-GEOD-70590 | biostudies-arrayexpress
Project description:Many cellular stresses cause damages of intracellular proteins, which are eventually degraded by the ubiquitin and proteasome system. The proteasome is a multicatalytic protease complex composed of 20S core particle and the proteasome activators that regulate the proteasome activity. Extracellular mutants 29 (Ecm29) is a 200 kDa protein encoded by KIAA0368 gene, associates with the proteasome, but its role is largely unknown. Here, we generated KIAA0368-deficient mice and investigated the function of Ecm29 in stress response. KIAA0368-deficient mice showed normal peptidase activity and proteasome formation at normal condition. Under stressed condition, 26S proteasome dissociates in wild-type cells, but not in KIAA0368(-/-) cells. This response was correlated with efficient degradation of damaged proteins and resistance to oxidative stress of KIAA0368(-/-) cells. Thus, Ecm29 is involved in the dissociation process of 26S proteasome, providing clue to analyse the mechanism of proteasomal degradation under various stress condition.
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Project description:Increased cellular levels of oxidative stress are implicated in a large number of human diseases. Here we describe the transcription co-factor KDM5 (also known as Lid) as a new critical regulator of cellular redox state. Moreover, this occurs through a novel KDM5 activity whereby it alters the ability of the transcription factor Foxo to bind to DNA. Our microarray analyses of kdm5 mutants revealed a striking enrichment for genes required to regulate cellular levels of oxidative stress. Consistent with this, loss of kdm5 results in increased sensitivity to treatment with oxidizers, elevated levels of oxidized proteins, and increased mutation load. KDM5 activates oxidative stress resistance genes by interacting with Foxo to facilitate its recruitment to KDM5-Foxo co-regulated genes. Significantly, this occurs independently of KDM5's well-characterized demethylase activity. Instead, KDM5 interacts with the lysine deacetylase HDAC4 to promote Foxo deacetylation, which affects Foxo DNA binding.
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