Dense Bicoid Hubs Accentuate Binding along the Morphogen Gradient

Mustafa MirArmando ReimerJenna E. HainesXiao-Yong LiMichael StadlerHernan G. GarciaMichael E. Eisen and Xavier Darzacq: Dense Bicoid Hubs Accentuate Binding along the Morphogen Gradient

Abstract: 

Morphogen gradients direct the spatial patterning of developing embryos, however, the mechanisms by which these gradients are interpreted remain elusive. Here we perform in vivo single molecule imaging of the transcription factor Bicoid that forms a gradient along the anteroposterior axis of the early Drosophila melanogaster embryo. We observe that Bicoid binds to DNA with a rapid off-rate, such that its average occupancy at target loci becomes on-rate dependent, a property required for concentration-sensitive regulation. Surprisingly, we also observe abundant specific DNA binding in posterior nuclei, where Bicoid levels are vanishingly low. Live embryo imaging reveals "hubs" of local high Bicoid concentration that are dependent on the ubiquitous maternal factor Zelda. We propose that localized modulation of transcription factor on-rates via clustering provides a general mechanism to facilitate binding to low-affinity targets under limiting factor conditions, and that this may be a prevalent feature directing other developmental transcription networks.