Hybridization led to a rewired pluripotency network in the allotetraploid Xenopus laevis

Abstract

After fertilization, maternally contributed factors to the egg initiate the transition to pluripotency to give rise to embryonic stem cells, in large part by activating de novo transcription from the embryonic genome. Diverse mechanisms coordinate this transition across animals, suggesting that pervasive regulatory remodeling has shaped the earliest stages of development. Here, we show that maternal homologs of mammalian pluripotency reprogramming factors OCT4 and SOX2 divergently activate the two subgenomes of Xenopus laevis, an allotetraploid that arose from hybridization of two diploid species ~18 million years ago. Although most genes have been retained as two homeologous copies, we find that a majority of them undergo asymmetric activation in the early embryo. Chromatin accessibility profiling and CUT&RUN for modified histones and transcription factor binding reveal extensive differences in predicted enhancer architecture between the subgenomes, which likely arose through genomic disruptions as a consequence of allotetraploidy. However, comparison with diploid X. tropicalis and zebrafish shows broad conservation of embryonic gene expression levels when divergent homeolog contributions are combined, implying strong selection to maintain dosage in the core vertebrate pluripotency transcriptional program, amid genomic instability following hybridization.

Data availability

All data and analysis files are available with no restrictions on access. Sequencing data are available in the Gene Expression Omnibus (GEO) under accession number GSE207027. Code and auxiliary data files are available on Github, github.com/MTLeeLab/xl-zga. Additional data files including chromosome alignments are available at OSF, osf.io/ct6g8/

The following data sets were generated
    1. Phelps WA
    2. Lee MT
    (2022) Xenopus MZT
    OSF, DOI 10.17605/OSF.IO/CT6G8.
The following previously published data sets were used

Article and author information

Author details

  1. Wesley A Phelps

    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4056-2345
  2. Matthew D Hurton

    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Taylor N Ayers

    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0680-0773
  4. Anne E Carlson

    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2724-1325
  5. Joel C Rosenbaum

    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Miler T Lee

    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States
    For correspondence
    miler@pitt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0933-0551

Funding

National Institutes of Health (R35GM137973)

  • Miler T Lee

March of Dimes Foundation (5-FY16-307)

  • Miler T Lee

Samuel and Emma Winters Foundation

  • Miler T Lee

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

Ethics

Animal experimentation: All animal procedures were conducted under the supervision and approval of the Institutional Animal Care and Use Committee at the University of Pittsburgh under protocol #21120500.

Copyright

© 2023, Phelps 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. Wesley A Phelps
  2. Matthew D Hurton
  3. Taylor N Ayers
  4. Anne E Carlson
  5. Joel C Rosenbaum
  6. Miler T Lee
(2023)
Hybridization led to a rewired pluripotency network in the allotetraploid Xenopus laevis
eLife 12:e83952.
https://doi.org/10.7554/eLife.83952

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https://doi.org/10.7554/eLife.83952

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