Transposable Elements Continuously Remodel the Regulatory Landscape, Transcriptome, and Function of Decidual Stromal Cells

Author:

Mika Katelyn1,Lynch Vincent J2ORCID

Affiliation:

1. Department of Human Genetics, The University of Chicago , 920 East 58th Street, CLSC 319C, Chicago, Illinois 60637 , USA

2. Department of Biological Sciences, University at Buffalo , SUNY, 551 Cooke Hall, Buffalo, New York 14260 , USA

Abstract

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 (DSCs) contributed to the origins of pregnancy in eutherians and the divergence of pregnancy traits in primates and that transposable elements likely contributed to these gene expression changes. Here we show that two large waves of TEs remodeled the transcriptome and regulatory landscape of DSCs, 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 that nearly all of them acted as repressors in mammalian cells, but treatment with a histone deacetylase inhibitor unmasked latent enhancer functions. These data indicate that TEs have played an important role in the development, evolution, and function of primate DSCs and suggest a two-step model in which latent enhancer functions of TEs are unmasked after they lose primary repressor functions.

Publisher

Oxford University Press (OUP)

Subject

Genetics,Ecology, Evolution, Behavior and Systematics

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