Quantitative dissection of transcription in development yields evidence for transcription factor-driven chromatin accessibility

Elizabeth Eck, Jonathan Liu, Maryam Kazemzadeh-Atoufi, Sydney Ghoreishi, Shelby Blythe, Hernan G. Garcia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Jan 28 2020

Keywords

  • Bicoid
  • Chromatin
  • Drosophila melanogaster
  • Hunchback
  • Live-imaging
  • Non-equilibrium models
  • Pioneer-factor
  • Thermodynamic models
  • Transcription
  • Zelda

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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