1. Physics of Living Systems
Download icon

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

  1. Elizabeth Eck
  2. Jonathan Liu
  3. Maryam Kazemzadeh-Atoufi
  4. Sydney Ghoreishi
  5. Shelby A Blythe
  6. Hernan G Garcia  Is a corresponding author
  1. University of California, Berkeley, United States
  2. Northwestern University, United States
Research Article
  • Cited 0
  • Views 891
  • Annotations
Cite this article as: eLife 2020;9:e56429 doi: 10.7554/eLife.56429

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.

Article and author information

Author details

  1. Elizabeth Eck

    Biophysics, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jonathan Liu

    Physics, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0204-0105
  3. Maryam Kazemzadeh-Atoufi

    Materials Science and Engineering, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sydney Ghoreishi

    Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Shelby A Blythe

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4986-2579
  6. Hernan G Garcia

    Molecular and Cell Biology, Physics, University of California, Berkeley, Berkeley, United States
    For correspondence
    hggarcia@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5212-3649

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

  1. Pierre Sens, Institut Curie, PSL Research University, CNRS, France

Publication history

  1. Received: February 27, 2020
  2. Accepted: October 16, 2020
  3. Accepted Manuscript published: October 19, 2020 (version 1)

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.

Metrics

  • 891
    Page views
  • 208
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cell Biology
    2. Physics of Living Systems
    Ishier Raote et al.
    Research Advance Updated

    The endoplasmic reticulum (ER)-resident protein TANGO1 assembles into a ring around ER exit sites (ERES), and links procollagens in the ER lumen to COPII machinery, tethers, and ER-Golgi intermediate compartment (ERGIC) in the cytoplasm (Raote et al., 2018). Here, we present a theoretical approach to investigate the physical mechanisms of TANGO1 ring assembly and how COPII polymerization, membrane tension, and force facilitate the formation of a transport intermediate for procollagen export. Our results indicate that a TANGO1 ring, by acting as a linactant, stabilizes the open neck of a nascent COPII bud. Elongation of such a bud into a transport intermediate commensurate with bulky procollagens is then facilitated by two complementary mechanisms: (i) by relieving membrane tension, possibly by TANGO1-mediated fusion of retrograde ERGIC membranes and (ii) by force application. Altogether, our theoretical approach identifies key biophysical events in TANGO1-driven procollagen export.

    1. Evolutionary Biology
    2. Physics of Living Systems
    Seyed Saeed Asadzadeh et al.
    Research Article

    Sponges are suspension feeders that filter vast amounts of water. Pumping is carried out by flagellated chambers that are connected to an inhalant and exhalant canal system. In 'leucon' sponges with relatively high-pressure resistance due to a complex and narrow canal system, pumping and filtering are only possible owing to the presence of a gasket-like structure (forming a canopy above the collar filters). Here we combine numerical and experimental work, and demonstrate how sponges that lack such sealing elements are able to efficiently pump and force the flagella driven flow through their collar filter, thanks to the formation of a 'hydrodynamic gasket' above the collar. Our findings link the architecture of flagellated chambers to that of the canal system, and lend support to the current view that the sponge aquiferous system evolved from an open-type filtration system, and that the first metazoans were filter feeders.