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 ofhunchbackby the activator Bicoid and the pioneer-like transcription factor Zelda in livingDrosophilaembryos and showed that no thermodynamic or non-equilibrium MWC model can recapitulatehunchbacktranscription. 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 predicthunchbackdynamics. 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 19, 2020
- Source ID
- 10.7554/elife.56429
Entities
People
- Elizabeth Eck
- Hernan G. Garcia
- Jonathan Liu
- Maryam Kazemzadeh-atoufi
- Shelby A. Blythe
- Sydney Ghoreishi
Organizations
- Burroughs Wellcome Fund
- Hellman Foundation
- Human Frontier Science Program
- National Institutes of Health
- National Science Foundation
- Northwestern University
- Shurl and Kay Curci Foundation
- United States Department of Defense
- University of California, Berkeley