Dense Bicoid hubs accentuate binding along the morphogen gradient
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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 used lattice light-sheet microscopy to 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. In contrast to canonical models, we observed that Bicoid binds to DNA with a rapid off rate throughout the embryo such that its average occupancy at target loci is on-rate-dependent. We further observed Bicoid forming transient “hubs” of locally high density that facilitate binding as factor levels drop, including in the posterior, where we observed Bicoid binding despite vanishingly low protein levels. 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 of other developmental transcription factors.
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Zelda promotes the formation of local transcription factor hubs involving transcription factors required for developmental patterning, such as Bicoid and Dorsal.
“For instance, Zelda promotes the formation of local TF hubs involving important transcription factors required for developmental patterning, such as Bicoid and Dorsal [51–54].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [51]
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“5 s−1 to ensure consistency with recent experimental measurements of Bicoid in [45, 46].”
BackgroundMethodInfluentialTranscriptional enhancers and their communication with gene promoters
Ray-Jones, H., & Spivakov, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03903-w · Cited by 81 · see citing works
- Authors
- Mir, M., Reimer, A., Haines, J. E., Li, X.-Y., Stadler, M., Garcia, H., Eisen, M. B., & Darzacq, X.
- Affiliations
- University of California, Berkeley (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Darzacq, Xavier
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2017-09-01
- Volume
- 31
- Issue
- 17
- Pages
- 1784-1794
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC5666676
- OpenAlex
- W2950013332
- Cited by
- 192
- References
- 3
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 24 · 2023: 27 · 2022: 24 · 2021: 20 · 2020: 22 · 2019: 19 · 2018: 22 · 2017: 5
- Type
- posted content
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Genes & Development (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- HighWire Press Open Archive (submittedVersion)
- Funders
- California Institute of Regenerative Medicine (LA1-08013)
- National Institutes of Health (UO1-EB021236, U54-DK107980)
- Burroughs Wellcome Fund
- Sloan Research Foundation
- Shurl and Kay Curci Foundation
- Howard Hughes Medical Institute
- National Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Keywords
- Bicoid, morphogen gradients, transcription factor-DNA binding, binding kinetics, protein clustering, anterior-posterior patterning, Drosophila melanogaster embryo, single-molecule imaging
- MeSH terms
- Single Molecule Imaging, Animals, Chromatin, Drosophila melanogaster, Embryo, Nonmammalian, Nuclear Proteins, Protein Binding, Transcription Factors, Trans-Activators, Homeodomain Proteins, Body Patterning, Drosophila Proteins
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