PT - JOURNAL ARTICLE AU - Mustafa Mir AU - Armando Reimer AU - Jenna E. Haines AU - Xiao-Yong Li AU - Michael Stadler AU - Hernan Garcia AU - Michael B. Eisen AU - Xavier Darzacq TI - Dense Bicoid Hubs Accentuate Binding along the Morphogen Gradient AID - 10.1101/133124 DP - 2017 Jan 01 TA - bioRxiv PG - 133124 4099 - http://biorxiv.org/content/early/2017/06/08/133124.short 4100 - http://biorxiv.org/content/early/2017/06/08/133124.full AB - 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 in early Drosophila melanogaster embryos of the transcription factor Bicoid that forms a gradient and initiates patterning along the anteroposterior axis. We observe that Bicoid binds to DNA with a rapid off-rate, such that its average occupancy at target loci is 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 spatiotemporal “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, and that this may be a prevalent feature directing other developmental transcription networks.