Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals.

A fundamental challenge in biology is explaining the origin of novel phenotypic characters such as new cell types; the molecular mechanisms that give rise to novelties are unclear. We explored the gene regulatory landscape of mammalian endometrial cells using comparative RNA-Seq and found that 1,532 genes were recruited into endometrial expression in placental mammals, indicating that the evolution of pregnancy was associated with a large-scale rewiring of the gene regulatory network. About 13% of recruited genes are within 200 kb of a Eutherian-specific transposable element (MER20). These transposons have the epigenetic signatures of enhancers, insulators and repressors, directly bind transcription factors essential for pregnancy and coordinately regulate gene expression in response to progesterone and cAMP. We conclude that the transposable element, MER20, contributed to the origin of a novel gene regulatory network dedicated to pregnancy in placental mammals, particularly by recruiting the cAMP signaling pathway into endometrial stromal cells.