Quantitative dissection of transcription in development yields evidence for transcription factor-driven chromatin accessibility
Abstract
Thermodynamic models of gene regulation can predict transcriptional regulation in bacteria, but in eukaryotes chromatin accessibility and energy expenditure may call for a different framework. Here we systematically tested the predictive power of models of DNA accessibility based on the Monod-Wyman-Changeux (MWC) model of allostery, which posits that chromatin fluctuates between accessible and inaccessible states. We dissected the regulatory dynamics of hunchback by the activator Bicoid and the pioneer-like transcription factor Zelda in living Drosophila embryos and showed that no thermodynamic or non-equilibrium MWC model can recapitulate hunchback transcription. Therefore, we explored a model where DNA accessibility is not the result of thermal fluctuations but is catalyzed by Bicoid and Zelda, possibly through histone acetylation, and found that this model can predict hunchback dynamics. Thus, our theory-experiment dialogue uncovered potential molecular mechanisms of transcriptional regulatory dynamics, a key step toward reaching a predictive understanding of developmental decision-making.
Data availability
Processed microscopy data have been deposited in Dryad (https://datadryad.org/stash/share/zakb7AqU2233pgWIs1mMAKyDiTQi4BXtnP0-Uu93xI0).
Article and author information
Author details
Funding
National Science Foundation (Graduate Student Fellowship)
- Elizabeth Eck
National Institutes of Health (DP2 OD024541-01)
- Hernan G Garcia
National Science Foundation (1652236)
- Hernan G Garcia
University of California, Berkeley (Chancellor's Fellowship)
- Elizabeth Eck
Department of Defense (Graduate Student Fellowship)
- Jonathan Liu
Burroughs Wellcome Fund (Career Award)
- Hernan G Garcia
Sloan Research Foundation
- Hernan G Garcia
Human Frontiers Science Program
- Hernan G Garcia
Searle Scholars Program
- Hernan G Garcia
Shurl and Kay Curci Foundation
- Hernan G Garcia
Hellman Foundation
- Hernan G Garcia
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Pierre Sens, Institut Curie, PSL Research University, CNRS, France
Version history
- Received: February 27, 2020
- Accepted: October 16, 2020
- Accepted Manuscript published: October 19, 2020 (version 1)
- Version of Record published: December 15, 2020 (version 2)
Copyright
© 2020, Eck et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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