Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Abrupt scrib- vs. Abrupt and RasV12 (RasACT) scrib-, NotchICD (NACT) scrib- +/- JNK (Bsk) expression profiles

ABSTRACT: Drosophila mosaic eye-antennal discs from the listed genotypes generated using the MARCM system were dissected from 3rd instar larvae at day 5 after egg deposition. 20 pairs of discs for the Abrupt and scrib- + Abrupt samples and 50 pairs from FRT control, NACT scrib- +/- BskDN and RasACT scrib- +/- BskDN were used to prepare RNA. Samples were prepared in triplicate, and the RNA isolated using TRIZOL, before being column purified (Qiagen). Probes were hybridized to GeneChip Drosophila 2.0 Genome Arrays (Affymetrix). To compare the expression profile of Abrupt when overexpressed in the eye-antennal discs with tumours formed by Abrupt overexpression in scrib- clones, and to reveal JNK responsive genes in RasV12 (RasACT) scrib- versus NotchICD (NACT) scrib- eye-antennal mosaic discs

ORGANISM(S): Drosophila melanogaster

SUBMITTER: Helena Richardson

PROVIDER: E-GEOD-42938 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in Drosophila melanogaster through maintaining a progenitor-like cell state.

Turkel Nezaket N Sahota Virender K VK Bolden Jessica E JE Goulding Karen R KR Doggett Karen K Willoughby Lee F LF Blanco Enrique E Martin-Blanco Enrique E Corominas Montserrat M Ellul Jason J Aigaki Toshiro T Richardson Helena E HE Brumby Anthony M AM

PLoS genetics 20130718 7

The capacity of tumour cells to maintain continual overgrowth potential has been linked to the commandeering of normal self-renewal pathways. Using an epithelial cancer model in Drosophila melanogaster, we carried out an overexpression screen for oncogenes capable of cooperating with the loss of the epithelial apico-basal cell polarity regulator, scribbled (scrib), and identified the cell fate regulator, Abrupt, a BTB-zinc finger protein. Abrupt overexpression alone is insufficient to transform ...[more]

PMID: 23874226

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Project description:Genomic enhancers regulate spatio-temporal gene expression by recruiting specific combinations of transcription factors (TFs). When TFs are bound to active regulatory regions, they displace canonical nucleosomes, making these regions biochemically detectable as nucleosome-depleted regions or accessible/open chromatin. Here we ask whether open chromatin profiling can be used to identify the entire repertoire of active promoters and enhancers underlying tissue-specific gene expression during normal development and oncogenesis in vivo. To this end, we first compare two different approaches to detect open chromatin in vivo using the Drosophila eye primordium as a model system: FAIRE-seq, based on physical separation of open versus closed chromatin; and ATAC-seq, based on preferential integration of a transposon into open chromatin. We find that both methods reproducibly capture the tissue-specific chromatin activity of regulatory regions, including promoters, enhancers, and insulators. Using both techniques, we screened for regulatory regions that become ectopically active during Ras-dependent oncogenesis, and identified 3778 regions that become (over-)activated during tumor development. Next, we applied motif discovery to search for candidate transcription factors that could bind these regions and identified AP-1 and Stat92E as key regulators. We validated the importance of Stat92E in the development of the tumors by introducing a loss of function Stat92E mutant, which was sufficient to rescue the tumor phenotype. Additionally we tested if the predicted Stat92E responsive regulatory regions are genuine, using ectopic induction of JAK/STAT signaling in developing eye discs, and observed that similar chromatin changes indeed occurred. Finally, we determine that these are functionally significant regulatory changes, as nearby target genes are up- or down-regulated. In conclusion, we show that FAIRE-seq and ATAC-seq based open chromatin profiling, combined with motif discovery, is a straightforward approach to identify functional genomic regulatory regions, master regulators, and gene regulatory networks controlling complex in vivo processes. FAIRE-Seq in Drosophila wild type eye-antennal imaginal discs (2 wt strains); ATAC-Seq in Drosophila wild type eye-antennal imaginal discs (3 wt strains) ; FAIRE-Seq in Drosophila Ras/Scrib induced eye disc tumors (1 early and 1 late); ATAC-Seq in Drosophila Ras/Scrib induced eye disc tumors (1 early and 1 late); ATAC-Seq in Drosophila eye discs with Unpaired over-expression (2 biological replicates); CTCF ChIP-seq in Drosophila eye discs; ChIP-seq input in Drosophila eye discs

Dataset Information

Abrupt scrib- vs. Abrupt and RasV12 (RasACT) scrib-, NotchICD (NACT) scrib- +/- JNK (Bsk) expression profiles

Publications

The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in Drosophila melanogaster through maintaining a progenitor-like cell state.

Similar Datasets

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