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| Status |
Public on Aug 01, 2024 |
| Title |
The JNK and Hippo pathways control epithelial integrity and prevent tumour initiation by regulating an overlapping transcriptome [DamID-seq] |
| Organism |
Drosophila melanogaster |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Epithelial organs maintain their integrity and prevent tumour initiation by actively removing defective cells, such as those that have lost apicobasal polarity. Here, we identify how transcription factors of two key signalling pathways – Jun-N-terminal kinase (JNK) and Hippo – regulate epithelial integrity by controlling transcription of an overlapping set of target genes. Targeted DamID experiments reveal that in proliferating cells of the Drosophila melanogaster eye, the AP-1 transcription factor Jun, and the Hippo pathway transcription regulators Yorkie and Scalloped bind to a common suite of target genes that regulate organ growth. In defective neoplastic cells, AP-1 transcription factors repress transcription of growth genes together with the CtBP co-repressor. If gene repression by AP-1/CtBP fails, neoplastic tumour growth ensues, driven by Yorkie/Scalloped. Thus, AP-1/CtBP eliminates defective cells and prevents tumour initiation by acting in parallel to Yorkie/Scalloped to repress expression of a shared transcriptome. These findings shed new light on the maintenance of epithelial integrity and tumour suppression.
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| Overall design |
Targeted DamID sequencing of Dam control, Yki-Dam, Dam-Sd and Dam-Jun fusions in Drosophila early third instar larval eye-antennal discs (3 replicates each)
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| Contributor(s) |
Mitchell KA, Vissers JH, Pojer JM, Brooks E, Jabbar Saiful Hilmi A, Papenfuss AT, Schröder J, Harvey KF |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jul 30, 2024 |
| Last update date |
Aug 01, 2024 |
| Contact name |
Kieran Harvey |
| E-mail(s) |
[email protected]
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| Organization name |
Peter MacCallum Cancer Centre
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| Department |
Research
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| Lab |
Kieran Harvey
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| Street address |
305 Grattan Street
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| City |
Melbourne |
| State/province |
Victoria |
| ZIP/Postal code |
3000 |
| Country |
Australia |
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| Platforms (1) |
| GPL19132 |
Illumina NextSeq 500 (Drosophila melanogaster) |
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| Samples (18)
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| GSM8428645 |
Eye-antennal disc, Eyeless-Gal4 Dam Replicate 1 (Set 1) |
| GSM8428646 |
Eye-antennal disc, Eyeless-Gal4 Dam Replicate 2 (Set 1) |
| GSM8428647 |
Eye-antennal disc, Eyeless-Gal4 Dam Replicate 3 (Set 1) |
| GSM8428648 |
Eye-antennal disc, Eyeless-Gal4 Dam-Sd Replicate 1 (Set 1) |
| GSM8428649 |
Eye-antennal disc, Eyeless-Gal4 Dam-Sd Replicate 2 (Set 1) |
| GSM8428650 |
Eye-antennal disc, Eyeless-Gal4 Dam-Sd Replicate 3 (Set 1) |
| GSM8428651 |
Eye-antennal disc, Eyeless-Gal4 Dam Replicate 1 (Set 2) |
| GSM8428652 |
Eye-antennal disc, Eyeless-Gal4 Dam Replicate 2 (Set 2) |
| GSM8428653 |
Eye-antennal disc, Eyeless-Gal4 Dam Replicate 3 (Set 2) |
| GSM8428654 |
Eye-antennal disc, Eyeless-Gal4 Yki-Dam Replicate 1 (Set 2) |
| GSM8428655 |
Eye-antennal disc, Eyeless-Gal4 Yki-Dam Replicate 2 (Set 2) |
| GSM8428656 |
Eye-antennal disc, Eyeless-Gal4 Yki-Dam Replicate 3 (Set 2) |
| GSM8428657 |
Eye-antennal disc, Eyeless-Gal4 Dam Replicate 1 (Set 3) |
| GSM8428658 |
Eye-antennal disc, Eyeless-Gal4 Dam Replicate 2 (Set 3) |
| GSM8428659 |
Eye-antennal disc, Eyeless-Gal4 Dam Replicate 3 (Set 3) |
| GSM8428660 |
Eye-antennal disc, Eyeless-Gal4 Dam-Jra Replicate 1 (Set 1) |
| GSM8428661 |
Eye-antennal disc, Eyeless-Gal4 Dam-Jra Replicate 2 (Set 1) |
| GSM8428662 |
Eye-antennal disc, Eyeless-Gal4 Dam-Jra Replicate 3 (Set 1) |
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| Relations |
| BioProject |
PRJNA1141937 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE273449_DamIDcounts.csv.gz |
18.0 Mb |
(ftp)(http) |
CSV |
| GSE273449_jun_peaks_filtered.togene.txt.gz |
150.8 Kb |
(ftp)(http) |
TXT |
| GSE273449_sd_peaks_filtered.togene.txt.gz |
163.1 Kb |
(ftp)(http) |
TXT |
| GSE273449_yki_peaks_filtered.togene.txt.gz |
126.8 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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