PT  - JOURNAL ARTICLE
AU  - Olga Zaytseva
AU  - Naomi C. Mitchell
AU  - Caroline Delandre
AU  - Zuqin Nie
AU  - Maurits Evers
AU  - Janis K. Werner
AU  - John T. Lis
AU  - Ross D. Hannan
AU  - David L. Levens
AU  - Owen J. Marshall
AU  - Leonie M. Quinn
TI  - Psi promotes <em>Drosophila</em> wing growth through transcriptional repression of key developmental networks
AID  - 10.1101/2020.05.13.094664
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.13.094664
4099  - http://biorxiv.org/content/early/2020/05/15/2020.05.13.094664.short
4100  - http://biorxiv.org/content/early/2020/05/15/2020.05.13.094664.full
AB  - Psi, the sole FUSE Binding Protein (FUBP) family single stranded DNA/RNA binding protein in Drosophila, is essential for proper cell and tissue growth, however its mechanism of function remains unclear. Here we use Targeted DamID combined with RNA-sequencing to generate the first genome-wide binding and expression profiles for Psi. Surprisingly, we demonstrate Psi drives growth in the Drosophila wing through transcriptional repression of key developmental pathways (e.g. Wnt, Notch and TGFβ). Thus, Psi patterns tissue growth by directly repressing transcription of developmental growth suppressors. Analysis of direct Psi targets identified novel growth inhibitors, including Tolkin (Zinc metallopeptidase implicated in TGFβ signalling), Ephexin (Rho-GEF) and emp (CD36 scavenger receptor-related protein). Their depletion not only suppressed impaired growth associated with Psi knockdown, but alone was sufficient to drive wing overgrowth. Thus, Psi drives wing growth twofold, through direct activation of Myc and through transcriptional repression of growth inhibitors comprising core developmental pathways.Competing Interest StatementThe authors have declared no competing interest.