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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptome perturbation analysis from 16 hours APF Drosophila notum.

ABSTRACT: Genome-wide transcriptome analysis of genetic pertubations induced in Drosophila notum by the over-expression of the transcription factors Achaete, Asense, E(spl)m3-HLH and Senseless. Transient over-expression of GFP (control), Achaete (Ac), Senseless (Sens), Asense (Ase) and E(spl)m3-HLH transcription factors in Drosophila notum using sca-Gal4, tub-Gal80ts. Transcription factorshave been over-expressed alone or in combinations. Three biological replicates were performed for each conditions.

ORGANISM(S): Drosophila melanogaster

SUBMITTER: francois schweisguth

PROVIDER: E-GEOD-53010 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcriptome perturbation analysis from 16 hours APF Drosophila notum.

Project description:Genome-wide transcriptome analysis of genetic pertubations induced in Drosophila notum by the over-expression of the transcription factors Achaete, Asense, E(spl)m3-HLH and Senseless.

2014-01-01 | GSE53010 | GEO

DamID profiling of proneural transcription factor binding in Drosophila melanogaster wing imaginal discs

Project description:Genome-wide identification of the binding sites of the Drosophila transcription factors Achaete, Asense, E(spl)m3-HLH and Senseless in wing imaginal cells using DamID profiling. Each Dam-fusion-derived sample is compared to a control Dam-only sample. Two biological replicates were performed for sca-Asense, neur-Asense, sca-Achaete, neur-Achaete, neur-Sens and sca-E(spl)m3-HLH.

2014-01-01 | E-GEOD-53009 | biostudies-arrayexpress

DamID profiling of proneural transcription factor binding in Drosophila melanogaster wing imaginal discs

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Control of neural daughter cell proliferation by multi-level Notch/Su(H)/E(spl)HLH signaling. (PMID: 27070787)

Project description:We expressed DamID and Flag-tagged versions of E(spl)HLH-m5, -m8 and Su(H), in Drosophila embryos and analyzed their DNA-binding by DamID-seq and ChIP-seq. The Notch pathway controls proliferation during development and in adulthood, and is frequently affected in many disorders. However, the genetic sensitivity and multi-layered transcriptional properties of the Notch pathway has made its molecular decoding challenging. Here, we address the complexity of Notch signaling with respect to proliferation, using the developing Drosophila CNS as model. We find that a Notch/Su(H)/E(spl)-HLH cascade specifically controls daughter, but not progenitor proliferation. Additionally, we find that different E(spl)-HLH genes are required in different neuroblast lineages. The Notch/Su(H)/E(spl)-HLH cascade alters daughter proliferation by regulating four key cell cycle factors: Cyclin E, String/Cdc25, E2f and Dacapo (mammalian p21CIP1/p27KIP1/p57Kip2). ChIP and DamID analysis of Su(H) and E(spl)-HLH indicates direct transcriptional regulation of the cell cycle genes, and of the Notch pathway itself. These results point to a multi-level signaling model, and may help shed light on the dichotomous proliferative role of Notch signaling in many other systems.

2019-09-11 | GSE137195 | GEO

Control ChIP-seq from whole organism (ENCSR782YFF)

Project description:Input control for ChIP-seq on transgenic flies expressing E(spl)m3-eGFP fusion proteins. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf

2024-02-27 | GSE258631 | GEO

TF ChIP-seq from whole organism (ENCSR671XAK)

Project description:ChIP-seq on transgenic flies expressing E(spl)m3-eGFP fusion proteins. The IP was performed using an anti-GFP antibody. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf

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Gene expression analysis of HepG2 cells by NOTUM RNAi

Project description:We identified human NOTUM, a new member of beta-catenin target gene. The aim of this analysis is to examine downstream genes of NOTUM. Keywords: Gene expression analysis in response to RNA interference HepG2 cells with RNAi duplexed were used. One control (control-low GC) and 2 RNAi duplexes (NOTUM RNAi#1 and #2) for NOTUM silencing were added to HepG2 cells, and total RNAs were isolated at 72 hours after transfection.

2011-03-15 | E-GEOD-6368 | biostudies-arrayexpress

Design of a potent, selective and brain penetrant inhibitor of Wnt-deactivating enzyme Notum by optimization of a crystallographic fragment hit

Project description:Notum is a carboxylesterase that suppresses Wnt signaling through deacylation of an essential palmitoleate group on Wnt proteins. There is a growing understanding of the role Notum plays in human disease such as colorectal cancer and Alzheimer’s disease supporting the need to discover improved inhibitors, especially for use in models of neurodegeneration. Here, we describe the discovery and profile of 8I (ARUK3001185) as a potent, selective and brain pentrant inhibitor of Notum activity suitable for oral dosing in rodent models of disease. Crystallographic fragment screening of the Diamond-SGC Poised Library for binding to Notum, supported by a biochemical enzyme assay to rank inhibition activity, identifed a pair of outstanding hits. Fragment development of these delivered 8I that restored Wnt signaling in the presence of Notum in a cell-based reporter assay. Assessment in proteomic and pharmacology screens showed 8I to be selective against serine hydrolases, kinases and drug targets.

2022-06-09 | PXD031338 | Pride

APC and P53 mutations synergize to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer [bulk RNA-seq]

Project description:We report that inactivation of the APC tumor suppressor results in dramatic activation of the NOTUM carboxylesterase, which has potent tumor suppressive activity in APC-null adenomatous epithelium. During progression to adenocarcinoma, APC and TP53 mutations (usually coincident in advanced CRC) synergize, converting NOTUM to an obligate oncoprotein. We provide evidence that the Jekyll-and-Hyde behavior of NOTUM results from its differential activity upon enzymatic targets Glypicans 1 and 4 in early vs. late-stage disease, respectively. Ultimately, we demonstrate that small molecule inhibition of NOTUM activity in a mouse model of metastatic colon cancer is sufficient to arrest primary tumor growth and metastatic colonization. Thus, the extracellular carboxylesterase NOTUM represents a novel therapeutic vulnerability in advanced colorectal adenocarcinomas.

2022-12-31 | GSE198757 | GEO

mRNA-seq of wild-type(N2), hlh-11 knock-out(KO) and hlh-11 over-expression(OE) worms

Project description:Purpose: Comparing the transcriptome of wild-type(N2), hlh-11 knock-out and hlh-11 over-expression worms to identify genes with differential expression. Methods: For each condition, two replicates were examined. For each sample, approximately 2,000 synchronized young adult worms were collected and resuspended in TRIzon Reagent (CW0580, CWBIO). Total RNA was isolated by chloroform extraction, followed by isopropanol precipitation. Sequencing was performed using HiSeq2500. The clean reads were aligned to WBcel235 genomes with TopHat2. Gene differential expression was analyzed using DEseq2. A threshold of p < 0.05 was set to determine differentially expressed genes. Induction (KO_up or OE_up) or suppression (KO_down or OE_down) of genes were obtained through comparing gene expressions in hlh-11 KO or OE worms to wild-type N2. Results: >86% reads were uniquely mapped. 2637 genes were significantly up regulated and 2845 genes were significantly down regulated in hlh-11 knock-out worms compared to wild-type. 107 genes were significantly up regulated and 237 genes were significantly down regulated in hlh-11 over-expression worms compared to wild-type. Conclusions: This study revealed the genes transcriptionally regulated by hlh-11.

2019-11-23 | GSE140866 | GEO

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