RT Journal Article
SR Electronic
T1 Control of Hox transcription factor concentration and cell-to-cell variability by an auto-regulatory switch
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 115220
DO 10.1101/115220
A1 Dimitrios K. Papadopoulos
A1 Kassiani Skouloudaki
A1 Ylva Engström
A1 Lars Terenius
A1 Rudolf Rigler
A1 Vladana Vukojević
A1 Pavel Tomancak
YR 2017
UL http://biorxiv.org/content/early/2017/03/14/115220.abstract
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.