PT - JOURNAL ARTICLE AU - Dimitrios K. Papadopoulos AU - Kassiani Skouloudaki AU - Ylva Engström AU - Lars Terenius AU - Rudolf Rigler AU - Vladana Vukojević AU - Pavel Tomancak TI - Control of Hox transcription factor concentration and cell-to-cell variability by an auto-regulatory switch AID - 10.1101/115220 DP - 2017 Jan 01 TA - bioRxiv PG - 115220 4099 - http://biorxiv.org/content/early/2017/03/14/115220.short 4100 - http://biorxiv.org/content/early/2017/03/14/115220.full AB - Concentration and DNA-binding kinetics of transcription factors (TFs) are crucial determinants of their function. Using Fluorescence Correlation Spectroscopy (FCS), we have characterized the concentration and cell-to-cell variability of 14 endogenously tagged TFs in live Drosophila imaginal discs. We found that variation in the concentration of different TFs among neighboring cells decreased with increasing average TF concentrations. Among the investigated TFs, Antennapedia (Antp), displayed the lowest average variability and transitioned from a low concentration/high variation state in second instar to a high concentration/low variation state in third instar imaginal discs. Using FCS and temporally resolved gain-and loss-of-function genetic studies we have uncovered that Antp is necessary and sufficient to drive a developmental regulatory switch from a state of auto-activation to a state of auto-repression. This mechanism is controlled by a progressive change in the relative concentrations of preferentially activating and repressing Antp isoforms that bind with different affinities to DNA.