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Dense Bicoid hubs accentuate binding along the morphogen gradient.

Mustafa Mir1, Armando Reimer2, Jenna E Haines1

  • 1Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California, 94720, USA.

Genes & Development
|October 7, 2017
PubMed
Summary

Transcription factor Bicoid (a key developmental protein) forms hubs, enhancing its DNA binding in fruit fly embryos. This mechanism helps pattern development even with low protein levels.

Keywords:
Bicoid, ZeldaDrosophilamorphogensingle-molecule fluorescencetranscription factor dynamics

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Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Morphogen gradients are crucial for embryonic spatial patterning.
  • The precise mechanisms of morphogen interpretation by transcription factors are not fully understood.

Purpose of the Study:

  • To investigate how the transcription factor Bicoid is interpreted in early Drosophila melanogaster embryos.
  • To elucidate the in vivo dynamics of Bicoid binding to DNA and its role in anteroposterior axis patterning.

Main Methods:

  • Utilized lattice light-sheet microscopy for in vivo single-molecule imaging.
  • Observed the behavior of the Bicoid transcription factor in early Drosophila melanogaster embryos.

Main Results:

  • Bicoid exhibits a rapid DNA off-rate, with binding dependent on the on-rate.
  • Transient, high-density Bicoid "hubs" were observed, facilitating DNA binding.
  • Bicoid binding was detected even at very low protein concentrations in the posterior embryo.

Conclusions:

  • Localized clustering of transcription factors (forming hubs) can enhance binding to low-affinity targets.
  • This hub-mediated mechanism may be a general strategy for other developmental transcription factors.
  • Challenges canonical models of morphogen gradient interpretation.