Epigenetic and non-epigenetic regulation of syncytin-1 expression in human placenta and cancer tissues

Cell Signal. 2014 Mar;26(3):648-56. doi: 10.1016/j.cellsig.2013.11.002. Epub 2013 Nov 9.

Abstract

Syncytin-1 is a human endogenous retroviral envelope gene (HERVW1) product specifically expressed in placental trophoblasts. By mediating the formation of syncytiotrophoblasts through cell-cell fusion, syncytin-1 plays a critical role for the placental barrier, endocrine and exchange functions. During pregnancy, syncytin-1 expression is dynamically regulated by various pathophysiological factors and pathways. This review summarizes and examines published data on epigenetic and non-epigenetic regulation of syncytin-1 gene expression, with a focus on the changes of syncytin-1 DNA methylation and expression in placental trophoblasts under preeclamptic and hypoxic conditions. The functions of syncytiotrophoblasts, the fusogenic and non-fusogenic activities of syncytin-1, and aberrant activation of syncytin-1 expression in cancer cells are also discussed. New findings on the epigenetic regulation of syncytin-1 in placentas from monozygotic/dichorionic discordant twins are analyzed. The close correlation among changes of DNMTs expression, syncytin-1 gene methylation, and syncytin-1 mRNA levels, in placentas associated with discordant fetal growth indicated a dynamic nature of syncytin-1 regulation.

Keywords: DNA Methylation; HERVW1, Preeclampsia; Non-fusogenic; Synctyine-1; Syncytiotrophoblast; Trophoblast.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Differentiation / genetics
  • Cell Fusion
  • Cell Hypoxia
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • DNA Methylation
  • DNA-Binding Proteins
  • Endogenous Retroviruses
  • Epigenesis, Genetic / genetics
  • Female
  • Fetal Growth Retardation / pathology
  • Gene Products, env / biosynthesis
  • Gene Products, env / genetics*
  • Humans
  • Neoplasms / metabolism*
  • Nuclear Proteins / metabolism
  • Placenta / metabolism*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Pregnancy Proteins / biosynthesis
  • Pregnancy Proteins / genetics*
  • RNA, Messenger / biosynthesis
  • Transcription Factors / metabolism
  • Trophoblasts / cytology
  • Trophoblasts / metabolism*
  • Twins, Monozygotic / genetics

Substances

  • DNA-Binding Proteins
  • GCM1 protein, human
  • Gene Products, env
  • Nuclear Proteins
  • Pregnancy Proteins
  • RNA, Messenger
  • Transcription Factors
  • syncytin
  • Cyclic AMP-Dependent Protein Kinases