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Transposable elements continuously remodel the regulatory landscape, transcriptome, and function of decidual stromal cells

View ORCID ProfileKatelyn Mika, View ORCID ProfileVincent J. Lynch
doi: https://doi.org/10.1101/2021.10.25.465769
Katelyn Mika
1Department of Human Genetics, The University of Chicago, 920 East 58th Street, CLSC 319C, Chicago, IL 60637, USA
2Department of Organismal Biology and Anatomy, University of Chicago, 1025 E 57th Street, Chicago, IL, 60637, USA
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Vincent J. Lynch
3Department of Biological Sciences, University at Buffalo, SUNY, 551 Cooke Hall, Buffalo, NY, 14260, USA
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  • For correspondence: vjlynch@buffalo.edu
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Abstract

Gene expression evolution underlies the origin, divergence, and conservation of biological characters including cell-types, tissues, and organ systems. Previously we showed that large-scale gene expression changes in decidual stromal cells contributed to the origins of pregnancy in eutherians and the divergence of pregnancy traits in primates (Marinić et al., 2021; Mika et al., 2021a, 2021b), and that transposable elements likely contributed to these gene expression changes (Mika et al., 2021a). Here we show that two large waves of TEs remodeled the transcriptome and regulatory landscape of decidual stromal cells, including a major wave in primates. Genes nearby TE-derived regulatory elements are among the most progesterone responsive in the genome and play essential roles in orchestrating progesterone responsiveness and the core function of decidual cells by donating progesterone receptor binding sites to the genome. We tested the regulatory abilities of 89 TE consensus sequences and found nearly all acted as repressors in mammalian cells but that treatment with histone deacetylase inhibitors unmasked latent enhancer functions. These data indicate TEs have played an important role in the development, evolution, and function of primate decidual stromal cells and suggest a two-step model in which latent enhancer functions of TEs are unmasked after they lose primary repressors functions.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted October 26, 2021.
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Transposable elements continuously remodel the regulatory landscape, transcriptome, and function of decidual stromal cells
Katelyn Mika, Vincent J. Lynch
bioRxiv 2021.10.25.465769; doi: https://doi.org/10.1101/2021.10.25.465769
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Transposable elements continuously remodel the regulatory landscape, transcriptome, and function of decidual stromal cells
Katelyn Mika, Vincent J. Lynch
bioRxiv 2021.10.25.465769; doi: https://doi.org/10.1101/2021.10.25.465769

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