Drosophila melanogaster
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA151497 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Analysis of the effects of ATM loss on gene expression to identify causes of neurodegeneration. ATM levels were reduced ubiquitously via the temperature-sensitive ATM^8 allele, or via tissue-specific RNAi of ATM (ATMi) using the Gal4/UAS expression system in neurons (Elav-GAL4 and ElavC155-GAL4) or glial cells (Repo-GAL4). A 20-chip study using total RNA representing 2 replicates of 3 control genotypes (ATM^8/+, Repo-GAL4, and ElavC155-GAL4) and 3 experimental genotypes (ATM^8/ATM^8, Repo-ATMi, ElavC155-ATMi), and 4 replicates each of a control (Elav-GAL4) and experimental (Elav-ATMi) genotype
2011-12-10 | E-GEOD-34315 | biostudies-arrayexpress
Project description:Analysis of the effects of ATM loss on gene expression to identify causes of neurodegeneration. ATM levels were reduced ubiquitously via the temperature-sensitive ATM^8 allele, or via tissue-specific RNAi of ATM (ATMi) using the Gal4/UAS expression system in neurons (Elav-GAL4 and ElavC155-GAL4) or glial cells (Repo-GAL4).
2011-12-10 | GSE34315 | GEO
Project description:The symptoms of ataxia-telangiectasia (A-T) include a progressive neurodegeneration caused by ATM protein deficiency. We previously found that nuclear accumulation of histone deacetylase-4, HDAC4, contributes to this degeneration; we now report that increased histone H3K27 trimethylation (H3K27me3) mediated by polycomb repressive complex 2 (PRC2) also plays an important role in the A-T phenotype. Enhancer of zeste homolog 2 (EZH2), a core catalytic component of PRC2, is identified as a new ATM kinase target, and its S734 phosphorylation reduces protein stability. Thus, PRC2 formation is elevated along with H3K27me3in ATM deficiency. ChIP-sequencing shows a significant increase in H3K27me3 ‘marks’ and a dramatic shift in their location. The change of H3K27me3 chromatin-binding pattern is directly related to cell cycle re-entry and cell death of ATM-deficient neurons. Lentiviral knockdown of EZH2 rescues Purkinje cell degeneration and behavioral abnormalities in Atm / mice, demonstrating that EZH2-mediated H3K27me3 is another key factor in A-T neurodegeneration. Two samples each were run of brain total RNA from Atm+/+ and Atm-/- mice.
2013-10-25 | E-GEOD-50951 | biostudies-arrayexpress
Project description:Polyglutamine Atrophin provokes neurodegeneration in Drosophila
| PRJNA135075 | ENA
Project description:A loss of the checkpoint kinase ATM leads to impairments in the DNA damage response, and in humans causes cerebellar neurodegeneration, and a high risk to cancer. A loss of ATM is also associated with increased protein aggregation. The relevance and characteristics of this aggregation are still incompletely understood. Moreover, it is unclear to what extent other genotoxic conditions can trigger protein aggregation as well. Here, we show that targeting ATM, but also ATR or DNA topoisomerases result in a similar, widespread aggregation of a metastable, disease-associated subfraction of the proteome. Aggregation-prone model substrates, including expanded polyglutamine repeats, aggregate faster under these conditions. This increased aggregation results from an overload of chaperone systems, which lowers the cell-intrinsic threshold for proteins to aggregate. In line with this, we find that inhibition of the HSP70 chaperone system further exacerbates the increased protein aggregation. Moreover, we identify the molecular chaperone HSPB5 as a potent suppressor of it. Our findings reveal that various genotoxic conditions trigger protein aggregation, in a manner that is highly reminiscent of the widespread aggregation occurring in situations of proteotoxic stress and in proteinopathies.
2022-02-07 | GSE173940 | GEO
Project description:The symptoms of ataxia-telangiectasia (A-T) include a progressive neurodegeneration caused by ATM protein deficiency. We previously found that nuclear accumulation of histone deacetylase-4, HDAC4, contributes to this degeneration; we now report that increased histone H3K27 trimethylation (H3K27me3) mediated by polycomb repressive complex 2 (PRC2) also plays an important role in the A-T phenotype. Enhancer of zeste homolog 2 (EZH2), a core catalytic component of PRC2, is identified as a new ATM kinase target, and its S734 phosphorylation reduces protein stability. Thus, PRC2 formation is elevated along with H3K27me3in ATM deficiency. ChIP-sequencing shows a significant increase in H3K27me3 ‘marks’ and a dramatic shift in their location. The change of H3K27me3 chromatin-binding pattern is directly related to cell cycle re-entry and cell death of ATM-deficient neurons. Lentiviral knockdown of EZH2 rescues Purkinje cell degeneration and behavioral abnormalities in Atm / mice, demonstrating that EZH2-mediated H3K27me3 is another key factor in A-T neurodegeneration.
2013-10-25 | GSE50951 | GEO
Project description:LATS1/2 are canonical Hippo signaling pathway components. Our genome-wide screen indicated a synthetic viable effect of Hippo pathway inhibition in ATM-depleted human embryonic and neural progenitor cells. This experiment was designed in order to get mechanistic insights regarding the molecular effect of Hippo pathway inhibition on ATM-knockout cells. Such chemical inhibition could potentially be used as a means to impede Ataxia-Telangiectasia-related neurodegeneration. Experimental procedure: 2 clones of ATM-knockout h-pES10 cells were plated on 6 well plates with MEFs feeder layer. 1 d after plating, medium was replaced with standard medium (as control) or medium containing 10 µM of LATS1/2 inhibitor, TRULI (Lats-IN-1) for 24 h. Cells were then harvested, total RNA was extracted, libraries for RNA sequencing were generated and sequenced. Total reads were mapped to human GRCh38 reference genome, and to mouse GRCm38 using STAR package. XenofilteR package in R was used to filter out mouse-originated reads. Count tables and differential analysis were performed using EdgeR package in R.
2024-01-10 | E-MTAB-12600 | biostudies-arrayexpress
Project description:Drosophila CNS OXPHOS inhibition microarray
| PRJNA379770 | ENA
Project description:Much focus has shifted towards understanding how glial dysfunction contributes to age-related neurodegeneration due to the crucial roles glial cells play in maintaining healthy brain function. Cell-cell interactions, which are largely mediated by cell-surface proteins, control many critical aspects of development and physiology; as such, dysregulation of glial cell-surface proteins in particular is hypothesized to play an important role in age-related neurodegeneration. However, it remains technically difficult to profile glial cell-surface proteins in intact brains. Here, we applied a cell-surface proteomic profiling method to glial cells from intact brains in Drosophila. Importantly, this enabled us to fully profile cell-surface proteomes in-situ, preserving native cell-cell interactions that would be omitted using more traditional proteomics methods. Applying this platform to young and old flies, we investigated how glial cell-surface proteomes change during aging. We identified candidate genes predicted to be involved in normal brain aging, including several associated with neural development and synapse wiring molecules not previously thought to be particularly active in glia. Through a functional genetic screen, we identified one surface protein, DIP-B, which is down-regulated in old flies and can increase fly lifespan when overexpressed in adult glial cells. We further performed whole-head single-nucleus RNA-seq, and revealed that DIP-B overexpression mainly impacts glial and fat cells. We also found that glial DIP-B overexpression was associated with improved cell-cell communication, which may contribute to the observed lifespan extension. Our study is the first to apply in-situ cell-surface proteomics to glial cells in Drosophila, and to identify DIP-B as a potential glial regulator of brain aging.
| MSV000099082 | MassIVE