TY - JOUR T1 - Transposable elements continuously remodel the regulatory landscape, transcriptome, and function of decidual stromal cells JF - bioRxiv DO - 10.1101/2021.10.25.465769 SP - 2021.10.25.465769 AU - Katelyn Mika AU - Vincent J. Lynch Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/10/26/2021.10.25.465769.abstract N2 - 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 StatementThe authors have declared no competing interest. ER -