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Series GSE59078 Query DataSets for GSE59078
Status Public on Feb 13, 2015
Title Discovery of Transcription Factors and Regulatory Regions Driving In Vivo Tumor Development by ATAC-seq and FAIRE-seq Open Chromatin Profiling
Organism Drosophila melanogaster
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
Overall design 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
Contributor(s) Davie K, Jacobs J, Potier D, Christiaens V, Aerts S
Citation(s) 25679813
Submission date Jul 03, 2014
Last update date May 15, 2019
Contact name Kristofer Davie
Organization name KU Leuven
Department Center for Human Genetics / VIB Center for Brain and Disease Research
Lab Lab of Computational Biology
Street address Herestraat 49 Bus 602
City Leuven
State/province Flemish-Brabant
ZIP/Postal code 3000
Country Belgium
Platforms (1)
GPL13304 Illumina HiSeq 2000 (Drosophila melanogaster)
Samples (13)
GSM1426254 FRT82_ATAC-Seq
GSM1426255 RAL-208_ATAC-Seq
GSM1426256 Optix-GFP_ATAC-Seq
BioProject PRJNA254336
SRA SRP044049

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Supplementary file Size Download File type/resource
GSE59078_All_ATAC-Seq_FAIRE-Seq.rawCounts.txt.gz 864.5 Kb (ftp)(http) TXT
GSE59078_All_ATAC-Seq_FAIRE-Seq_Merged_Peaks.bed.gz 392.4 Kb (ftp)(http) BED
GSE59078_RAW.tar 898.6 Mb (http)(custom) TAR (of BED, BW)
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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