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Dense Bicoid Hubs Accentuate Binding along the Morphogen Gradient

Mustafa Mir, Armando Reimer, Jenna E. Haines, Xiao-Yong Li, Michael Stadler, Hernan Garcia, Michael B. Eisen, Xavier Darzacq
doi: https://doi.org/10.1101/133124
Mustafa Mir
1 Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA
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Armando Reimer
2 Biophysics Graduate Group, University of California, Berkeley, CA, 94720, USA
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Jenna E. Haines
1 Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA
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Xiao-Yong Li
3 Howard Hughes Medical Institute, University of California, Berkeley, CA, 94720, USA
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Michael Stadler
1 Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA
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Hernan Garcia
1 Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA
2 Biophysics Graduate Group, University of California, Berkeley, CA, 94720, USA
4 Department of Physics, University of California, Berkeley, CA, 94720, USA
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Michael B. Eisen
1 Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA
2 Biophysics Graduate Group, University of California, Berkeley, CA, 94720, USA
3 Howard Hughes Medical Institute, University of California, Berkeley, CA, 94720, USA
5 Department of Integrative Biology, University of California, Berkeley, CA, 94720, USA
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Xavier Darzacq
1 Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA
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  • For correspondence: darzacq@berkeley.edu
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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 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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 08, 2017.
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Dense Bicoid Hubs Accentuate Binding along the Morphogen Gradient
Mustafa Mir, Armando Reimer, Jenna E. Haines, Xiao-Yong Li, Michael Stadler, Hernan Garcia, Michael B. Eisen, Xavier Darzacq
bioRxiv 133124; doi: https://doi.org/10.1101/133124
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Dense Bicoid Hubs Accentuate Binding along the Morphogen Gradient
Mustafa Mir, Armando Reimer, Jenna E. Haines, Xiao-Yong Li, Michael Stadler, Hernan Garcia, Michael B. Eisen, Xavier Darzacq
bioRxiv 133124; doi: https://doi.org/10.1101/133124

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