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Endogenous retroviruses facilitate lineage-specific evolution of human placental gene expression landscape

Wednesday, September 12, 2018 — Poster Session I

12:00 p.m. – 1:30 p.m.
FAES Terrace
NICHD
GEN-21

Authors

  • M Sun
  • G Wolf
  • C Dunn-Fletcher
  • L Muglia
  • T Macfarlan

Abstract

In mammals, the placenta is an organ crucial for fetus development by mediating nutrient and waste exchange between the mother and fetus. Although performs the same basic function in all mammals, it is fast evolving and highly diversified among different species. Emerging evidence suggests that endogenous retroviruses (ERVs) can promote genetic innovation by creating novel cis-elements. Recent study showed that a specific ERV family named RLTR13D5 contributes hundreds of mouse-specific enhancers underlying placenta regulatory network. However, the understanding about the molecular mechanism for the evolution of human placenta remains limited. In this study, we performed inter-species transcriptome and epigenome analyses among human, macaque and mouse placenta and other tissues. We identified hundreds of human-placenta-enriched genes – many are well-known factors essential for female pregnancy. Based on histone marks, thousands of human-placenta-specific cis-elements were annotated. Gaining of active cis-elements correlates with the lineage-specific expression of human-placenta-enriched genes. We further found that several ERV families are over-represented near both human-placenta-enriched genes and human-placenta-specific cis-elements - potentially mediating the evolution of placental gene expression by creating novel cis-elements. Interestingly, one of them, MER41B, was proposed recently been co-opted as enhancers for innate immunity system which is important for proper placenta development. In summary, this study represents the first systematic inter-species comparison of the placental transcriptome and epigenome between human and other mammalian species. Our results indicate placenta is diversified among mammalian species regarding transcription and epigenetic landscapes, and suggest the pervasive importance of ERVs for the lineage-specific evolution of placenta among mammalian species.

Category: Genetics and Genomics