How enhancers regulate wavelike gene expression patterns

  1. Christine Mau
  2. Heike Rudolf
  3. Frederic Strobl
  4. Benjamin Schmid
  5. Timo Regensburger
  6. Ralf Palmisano
  7. Ernst HK Stelzer
  8. Leila Taher  Is a corresponding author
  9. Ezzat El-Sherif  Is a corresponding author
  1. Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany
  2. Goethe Universität Frankfurt am Main, Germany
  3. Graz University of Technology, Austria
  4. The University of Texas Rio Grande Valley, United States

Abstract

A key problem in development is to understand how genes turn on or off at the right place and right time during embryogenesis. Such decisions are made by non-coding sequences called 'enhancers'. Much of our models of how enhancers work rely on the assumption that genes are activated de novo as stable domains across embryonic tissues. Such view has been strengthened by the intensive landmark studies of the early patterning of the anterior-posterior (AP) axis of the Drosophila embryo, where indeed gene expression domains seem to arise more or less stably. However, careful analysis of gene expression patterns in other model systems (including the AP patterning in vertebrates and short-germ insects like the beetle Tribolium castaneum) painted a different, very dynamic view of gene regulation, where genes are oftentimes expressed in a wavelike fashion. How such gene expression waves are mediated at the enhancer level is so far unclear. Here we establish the AP patterning of the short-germ beetle Tribolium as a model system to study dynamic and temporal pattern formation at the enhancer level. To that end, we established an enhancer prediction system in Tribolium based on time- and tissue-specific ATAC-seq and an enhancer live reporter system based on MS2 tagging. Using this experimental framework, we discovered several Tribolium enhancers, and assessed the spatiotemporal activities of some of them in live embryos. We found our data consistent with a model in which the timing of gene expression during embryonic pattern formation is mediated by a balancing act between enhancers that induce rapid changes in gene expression patterns (that we call 'dynamic enhancers') and enhancers that stabilizes gene expression patterns (that we call 'static enhancers'). However, more data is needed for a strong support for this or any other alternative models.

Data availability

Raw sequence files and scaled coverage tracks (in bigWig format) have been deposited in the Gene Expression Omnibus database under accession number GSE235410. Scaled coverage tracks were also uploaded to the iBeetleBase Genome Browser (https://ibeetle-base.uni-goettingen.de/genomebrowser/) (107). Matlab codes for the Speed Regulation and Enhancer Switching models can be found in (Kuhlmann L, El-Sherif E. Speed regulation and gradual enhancer switching models as flexible and evolvable patterning mechanisms. BioRxiv. 2018 Feb 7), and can be modified based on information and parameter values indicated in Materials and Methods (Computational Modeling) to generate the simulations presented in this study. Generated transgenic Tribolium lines are available upon request.

The following data sets were generated

Article and author information

Author details

  1. Christine Mau

    Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Heike Rudolf

    Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Frederic Strobl

    Buchmann Institute for Molecular Life Sciences, Goethe Universität Frankfurt am Main, Frankfurt am Main, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Benjamin Schmid

    Optical Imaging Centre Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9327-2296
  5. Timo Regensburger

    Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Ralf Palmisano

    Optical Imaging Centre Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4283-2115
  7. Ernst HK Stelzer

    Buchmann Institute for Molecular Life Sciences, Goethe Universität Frankfurt am Main, Frankfurt am Main, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1545-0736
  8. Leila Taher

    Institute of Biomedical Informatics, Graz University of Technology, Graz, Austria
    For correspondence
    leila.taher@tugraz.at
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2013-5426
  9. Ezzat El-Sherif

    Department of Biology, The University of Texas Rio Grande Valley, Edinburg, United States
    For correspondence
    ezzat.elsherif@utrgv.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1738-8139

Funding

Deutsche Forschungsgemeinschaft (EL 870/2-1)

  • Ezzat El-Sherif

Studienstiftung des Deutschen Volkes

  • Christine Mau

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Ariel D. Chipman, The Hebrew University of Jerusalem, Israel

Version history

  1. Preprint posted: September 10, 2022 (view preprint)
  2. Received: November 16, 2022
  3. Accepted: July 10, 2023
  4. Accepted Manuscript published: July 11, 2023 (version 1)
  5. Version of Record published: July 25, 2023 (version 2)

Copyright

© 2023, Mau 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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  1. Christine Mau
  2. Heike Rudolf
  3. Frederic Strobl
  4. Benjamin Schmid
  5. Timo Regensburger
  6. Ralf Palmisano
  7. Ernst HK Stelzer
  8. Leila Taher
  9. Ezzat El-Sherif
(2023)
How enhancers regulate wavelike gene expression patterns
eLife 12:e84969.
https://doi.org/10.7554/eLife.84969

Share this article

https://doi.org/10.7554/eLife.84969

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