Poster Presentation 16th Asian Conference on Transcription 2019

Psi, the Drosophila ortholog of the FUBP1 single stranded DNA binding protein, fine-tunes transcription of developmental patterning genes (1126)

Olga Zaytseva 1 2 , Linna Guo 1 2 , Naomi C Mitchell 1 , Caroline Delandre 3 , Owen J Marshall 3 , Ross D Hannan 1 4 , David L Levens 5 , Leonie M Quinn 1 2
  1. John Curtin School of Medical Research, Canberra, ACT, Australia
  2. The University of Melbourne, Parkville, VIC, Australia
  3. Menzies Institute for Medical Research, Hobart, TAS, Australia
  4. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  5. National Cancer Institute, NIH, Bethesda, Maryland, USA

The human Far Upstream Binding Protein 1 (FUBP1) was isolated over a quarter of a century ago due to capacity to bind the active MYC promoter, remodel single stranded DNA architecture, and enable maximal activation of MYC transcription. Consistent with this function, FUBP1 is upregulated in many cancers, including breast, liver, bladder, kidney and lung. However, the broader significance of FUBP family proteins in genome-wide transcriptional control and how such functions might regulate animal development has remained unclear. Our recent Drosophila studies revealed conserved functions for the FUBP1 ortholog (Psi) in controlling Myc transcription and promoting cell and tissue growth in the wing epithelium. We further demonstrated physical and genetic interaction with the Mediator (MED) complex, which likely enables integration of developmental signals at multiple promoters. Indeed, our exciting new data demonstrate that, in addition to Myc, Psi binds to multiple transcriptional targets in the wing epithelium in vivo. Intersection of RNA-seq to detect differentially expressed genes following Psi depletion, and wing-specific direct binding sites identified genome-wide by Targeted DamID, revealed a developmental patterning signature for Psi including Wnt, Notch and TGFβ cell fate determinant pathways. Moreover, analysis of direct Psi targets identified several novel growth regulators, including the TGFβ signalling regulator Tolkin and the RhoGEF Ephexin. Together our data suggest Psi integrates cellular signalling inputs to directly modulate transcriptional outputs and fine-tune development. Our current and future work aims to elucidate the mechanisms by which Psi remodels single-stranded DNA and restructures chromatin in vivo.