Hybridization led to a rewired pluripotency network in the allotetraploid Xenopus laevis
- University of Pittsburgh, United States
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/
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Hybridization led to a rewired pluripotency network in the allotetraploid Xenopus laevisNCBI Gene Expression Omnibus, GSE207027.
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Optimized design of antisense oligomers for targeted rRNA depletionNCBI Gene Expression Omnibus, GSE152902.
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Enhancer chromatin signatures predict Smad2/3 binding in XenopusNCBI Gene Expression Omnibus, GSE56000.
Article and author information
Author details
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.
Reviewing Editor
- Carole LaBonne, Northwestern University, United States
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.
Version history
- Preprint posted: September 17, 2022 (view preprint)
- Received: October 4, 2022
- Accepted: October 2, 2023
- Accepted Manuscript published: October 3, 2023 (version 1)
- Version of Record published: October 12, 2023 (version 2)
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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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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