Characterisation of the in-vivo miRNA landscape in Drosophila ribonuclease mutants reveals Pacman mediated regulation of the highly conserved let-7 cluster during apoptotic processes
Ontology highlight
ABSTRACT:
INSTRUMENT(S): NextSeq 500
ORGANISM(S): Drosophila melanogaster
SUBMITTER: Ben Towler
PROVIDER: E-MTAB-13781 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:RNA-seq on 120hr L3 larval wing imaginal discs. 3 replicates of dis3L2 null mutant, and 3 replicates of control wing discs. rRNA depleted, Illumina TruSeq libraries. Paired-end sequencing on a HiSeq 3000.
2021-10-18 | E-MTAB-7451 | biostudies-arrayexpress
Project description:We investigated the effect on mRNA expression in Drosophila melanogaster wing imaginal discs following the knockdown of the 3'-5' exoribonuclease Dis3L2.
2016-11-16 | E-MTAB-4545 | biostudies-arrayexpress
Project description:An analysis of the transcriptional profiles of weak genetic perturbations generated via P-elements measured as heterozygotes in wing imaginal discs of Drosophila melanogaster. Abstract: A major objective of genomics is to elucidate the mapping between genotypic and phenotypic space as a step toward understanding how small changes in gene function can lead to elaborate phenotypic changes. One approach that has been utilized is to examine overall patterns of co-variation between phenotypic variables of interest, such as morphology, physiology and behavior, and underlying aspects of gene activity, in particular transcript abundance on a genome wide scale. Numerous studies have demonstrated that such patterns of co-variation occur, although these are often between samples with large numbers of unknown genetic differences (different strains, or even species) or perturbations of large effect (sexual dimorphism, or strong loss of function mutations), that may represent physiological changes outside of the normal experiences of the organism. We used weak mutational perturbations in genes affecting wing development in Drosophila melanogaster, that influence wing shape relative to a co-isogenic wild-type. We profiled transcription of 1150 genes expressed during wing development in 27 heterozygous mutants, as well as their co-isogenic wild type and one additional wild-type strain. Despite finding clear evidence of expression differences between mutants and wild-type, transcriptional profiles did not co-vary strongly with shape, suggesting that information from transcriptional profiling may not generally be predictive of final phenotype. We discuss these results in the light of possible attractor states of gene expression, and how this would affect interpretation of co-variation between transcriptional profiles and other phenotypes. Total RNA was extracted from pools of wing imaginal discs for each mutant strain as well as for their co-isogenic wild-type, and one additional wild-type strain. RNA was extracted using a modified protocol using the Qiagen RNAeasy kit.
2011-01-19 | E-GEOD-26706 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-06-10 | E-GEOD-71354 | biostudies-arrayexpress
Project description:Histone H3 lysine27-to-methionine (H3K27M) gain-of-function mutations occur in highly aggressive pediatric gliomas. Here, we establish a Drosophila animal model for the pathogenic histone H3K27M mutation and show that its overexpression resembles Polycomb repressive complex 2 (PRC2) loss-of-function phenotypes, causing de-repression of PRC2 target genes and developmental perturbations. Similarly, a H3K9M mutant depletes H3K9 methylation levels and suppresses position-effect variegation in various Drosophila tissues. The histone H3K9 demethylase KDM3B/JHDM2 associates with H3K9M nucleosomes and its overexpression in Drosophila results in loss of H3K9 methylation levels and heterochromatic silencing defects. Here we establish histone lysine-to-methionine mutants as robust in vivo tools for inhibiting methylation pathways that also function as biochemical reagents for capturing site-specific histone-modifying enzymes, thus providing molecular insight into chromatin-signaling pathways. RNA-seq of wing imaginal discs expressing either H3.3WT-FLAG-HA or H3.3K27M-FLAG-HA.
2014-09-02 | E-GEOD-59891 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-02-07 | E-GEOD-43130 | biostudies-arrayexpress
Project description:We investigated the effect on miRNA expression in Drosophila melanogaster wing imaginal discs following the knockdown of the 3'-5' exoribonuclease Dis3.
2015-06-01 | E-MTAB-3569 | biostudies-arrayexpress
Project description:Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the main events participating in the healing of a wound, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila imaginal discs, do not model all aspects of the repair process, but allow exploring many unanswered features of the healing response; e.g., which are the signal(s) responsible for initiating tissue remodeling? How is the sealing of the epithelia achieved? Or which are the inhibitory cues that cancel the healing machinery upon completion? Answering these and other questions demands in first place the identification and functional analysis of wound-specific genes. A variety of different microarray analyses of murine and humans have identified characteristic profiles of gene expression at the wound site, however, very few functional studies in healing regulation have been carried out. We developed an experimentally controlled method to culture imaginal discs that allows live imaging and biochemical analysis and is healing-permissive. Employing this approach, we performed a comparative genome-wide profiling between those Drosophila imaginal cells actively involved in healing versus their non-engaged siblings. This lets us identify a set of potential wound-specific genes. Importantly, besides identifying and categorizing new genes, we functionally tested many of their gene products by genetic interference and overexpression in a healing assay. This non-saturated analysis defines a relevant set of new genes whose changes in expression levels are functionally significant for proper tissue repair. There is promise that our newly identified wound-healing genes will guide future work in the more complex mammalian wound response. We developed a healing-permissive in vitro culture system for fly imaginal discs: we used one-channel microarrays for comparing healing-engaged cells (showing activation of the JNK signaling cascade) to cells not participating in healing (silent JNK activity) in wounded wing imaginal discs in culture. Employing this method, we aimed detecting the relevant genes involved in disc healing through microarray analysis. We compared cells actively involved in healing to those not involved and identified a whole set of upregulated or downregulated genes. They were annotated, clustered by expression profiles, chromosomal locations and presumptive functions. Most importantly, we functionally tested them genetically in a healing assay.
2015-04-13 | E-GEOD-62863 | biostudies-arrayexpress
Project description:Cancer cells have abnormal gene expression profiles, however, the transcription factors and the architecture of the regulatory network that drive cancer specific gene expression is often not known. Here we studied a model of Ras-driven invasive tumorigenesis in Drosophila epithelial tissues and combined in vivo genetics with high-throughput sequencing and computational modeling to decipher the regulatory logic of tumor cells. Surprisingly, we discovered that the bulk of the tumor specific gene expression is driven by an ectopic network of a few transcription factors that are overexpressed and/or hyperactivated in tumor cells. These factors are Stat, AP-1, the bHLH proteins Myc and AP-4, the nuclear hormone receptor Ftz-f1, the nuclear receptor coactivator Taiman/AIB1, and Mef2. Notably, many of these transcription factors are also hyperactivated in human tumors. Bioinformatics analysis predicted that these factors directly regulate the majority of the tumor specific gene expression, that they are interconnected by extensive cross-regulation, and that they show a high degree of co-regulation of target genes. Indeed, the factors of this network were required in multiple epithelia for tumor growth and invasiveness and knock-down of individual factors caused a reversion of the tumor specific expression profile, but had no observable effect on normal tissues. We further found that the Hippo pathway effector Yki/Sd was strongly activated in tumor cells and initiated cellular reprogramming by activating several transcription factors of this network. Thus, modeling regulatory networks identified an ectopic yet highly ordered network of master regulators that control tumor cell specific gene expression. RNA-seq gene expression profiling across Drosophila 3rd instar larval wild type wing discs and genetic perturbations of wts.
2016-06-10 | E-GEOD-71353 | biostudies-arrayexpress
Project description:Cancer cells have abnormal gene expression patterns, however, the transcription factors and the architecture of the regulatory network that drive cancer specific gene expression profiles is often not known. Here we studied a model of Ras-driven invasive tumorigenesis in Drosophila larval epithelial tissues and combined in vivo genetic analyses with high-throughput sequencing and computational modeling to decipher the regulatory logic of tumor cells. Surprisingly, we discovered that tumor specific gene expression is driven by a highly interconnected network composed of few transcription factors. These are: Stat, Mef2, the AP-4 homolog Cropped, the nuclear receptor Ftz-f1, the bHLH factors Myc and Taiman, and the AP-1 transcription factors Kayak, ATF-3, Pdp1, and dCEBPG. Many of these transcription factors are ectopically expressed and/or hyperactivated in human tumors. The members of this tumor master regulatory network are predicted to directly regulate the majority of the tumor specific gene expression profile. Similar to networks of master regulators that control organ development and cellular differentiation, there is a predicted high degree of co-regulation of target genes, and these network members are required in multiple eptihelia for tumor growth and invasiveness. We further found that Yki/Sd and bZIP/AP-1 factors, the downstream transcription factors of the Hippo and JNK pathways, initiate cellular reprogramming by activating several transcription factors of this network. Thus, modeling regulatory networks identified an ectopic yet highly ordered network of master regulators that control cancer cell specific gene expression. RNA-seq gene expression profiling across Drosophila 3rd instar larval imaginal discs (eye-antenna, wing and leg) in a hh driven tumor model, perturbations and controls.
2016-06-10 | E-GEOD-81272 | biostudies-arrayexpress