RT Journal Article
SR Electronic
T1 Dense Bicoid Hubs Accentuate Binding along the Morphogen Gradient
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 133124
DO 10.1101/133124
A1 Mustafa Mir
A1 Armando Reimer
A1 Jenna E. Haines
A1 Xiao-Yong Li
A1 Michael Stadler
A1 Hernan Garcia
A1 Michael B. Eisen
A1 Xavier Darzacq
YR 2017
UL http://biorxiv.org/content/early/2017/06/08/133124.abstract
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.