Ratiometric sensing of Pnt and Yan transcription factor levels confers ultrasensitivity to photoreceptor fate transitions in Drosophila.
Sebastian M BernasekSuzy S J HurNicolás Peláez-RestrepoJean-François Boisclair LachanceRachael BakkerHeliodoro Tejedor NavarroNicelio Sanchez-LuegeLuís A Nunes AmaralNeda BagheriIlaria RebayRichard W CarthewPublished in: Development (Cambridge, England) (2023)
Cell state transitions are often triggered by large changes in the concentrations of transcription factors and therefore large differences in their stoichiometric ratios. Whether cells can elicit transitions using modest changes in the ratios of co-expressed factors is unclear. Here we investigate how cells in the Drosophila eye resolve state transitions by quantifying the expression dynamics of the ETS transcription factors Pnt and Yan. Eye progenitor cells maintain a relatively constant ratio of Pnt/Yan protein despite expressing both proteins with pulsatile dynamics. A rapid and sustained two-fold increase in the Pnt/Yan ratio accompanies transitions to photoreceptor fates. Genetic perturbations that modestly disrupt the Pnt/Yan ratio produce fate transition defects consistent with the hypothesis that transitions are normally driven by a two-fold shift in the ratio. A biophysical model based on cooperative Yan-DNA binding coupled with non-cooperative Pnt-DNA binding illustrates how two-fold ratio changes could generate ultrasensitive changes in target gene transcription to drive fate transitions. Thus, coupling cell state transitions to the Pnt/Yan ratio sensitizes the system to modest fold-changes, conferring robustness and ultrasensitivity to the developmental program.
Keyphrases
- transcription factor
- dna binding
- induced apoptosis
- genome wide identification
- cell cycle arrest
- poor prognosis
- single cell
- cell therapy
- gold nanoparticles
- quality improvement
- stem cells
- endoplasmic reticulum stress
- copy number
- nitric oxide
- mesenchymal stem cells
- oxidative stress
- genome wide
- long non coding rna
- signaling pathway
- room temperature
- high resolution
- living cells
- fluorescent probe
- bone marrow