| First Authors | Dimitrios Papadopoulos |
|---|---|
| Authors | Dimitrios Papadopoulos, Kassiani Skouloudaki, Ylva Engström, Lars Terenius, Rudolf Rigler, Christoph Zechner, Vladana Vukojević, Pavel Tomancak |
| Corresponding Authors | Dimitrios Papadopoulos, Pavel Tomancak |
| Last Authors | Pavel Tomancak |
| Journal Name | Development (Cambridge, England) (Development) |
| Volume | 146 |
| Issue | 12 |
| Article Number | dev168179 |
| PubMed ID | 30642837 |
| WebOfScience Link | |
| Open Access | false |
| Print Publication Date | 2019-01-25 |
| Online Publication Date | 2018-11-24 |
| Abstract | The variability in transcription factor concentration among cells is an important developmental determinant, yet how variability is controlled remains poorly understood. Studies of variability have focused predominantly on monitoring mRNA production noise. Little information exists about transcription factor protein variability, as this requires the use of quantitative methods with single-molecule sensitivity. Using Fluorescence Correlation Spectroscopy (FCS), we have characterized the concentration and variability of 14 endogenously tagged TFs in live Drosophila imaginal discs. For the Hox TF Antennapedia, we investigated whether protein variability results from random stochastic events or is developmentally regulated. We found that Antennapedia transitioned from low concentration/high variability early, to high concentration/low variability later, in development. FCS and temporally resolved genetic studies uncovered that Antennapedia itself is necessary and sufficient to drive a developmental regulatory switch from auto-activation to auto-repression, thereby reducing variability. This switch is controlled by progressive changes in relative concentrations of preferentially activating and repressing Antennapedia isoforms, which bind chromatin with different affinities. Mathematical modeling demonstrated that the experimentally supported auto-regulatory circuit can explain the increase of Antennapedia concentration and suppression of variability over time. |
| Cover Image | |
| Affiliated With | Knust, Postdoc first author, Postdocs, Tomancak, Zechner |
| Selected By | |
| Acknowledged Services | DNA Sequencing, Protein Expression, Light Microscopy Facility |
| Publication Status | Published |
| Edoc Link | |
| Sfx Link | |
| DOI | 10.1242/dev.168179 |
| Display Publisher Download Only | false |
| Visible On MPI-CBG Website | true |
| PDF Downloadable | true |
| Created By | verhegge |
| Added Date | 2018-11-28 |
| Last Edited By | verhegge |
| Last Edited Date | 2019-01-30 13:21:10.782 |
| Library ID | 7275 |
| Document ID | |
| Entry Complete | true |
| eDoc Compliant | true |
| Include in Edoc Report | true |
| Author Affiliations Complete | false |