The epigenetic control of HERV loci encoding for fusogenic envelope glycoproteins in trophoblast

Abstract

Background Up to 8% of the human genome is of retroviral origin, comprising numerous human endogenous retroviruses (HERVs), remnants of germ line transmission of exogenous retroviruses during primate and human evolution. Some endogenous retroviruses within the human genome remain intact open reading frames with translational potential. Gag and Env genes are often expressed in various human tissues and provide superantigens or restriction factors interfering with exogenous infections. Several Env products display fusogenic properties and it is temting to implicite them in various human pathologies like cancer, multiple sclerosis, and muscular dystrophies. Of particular importace are the fusogenic Env proteins expressed in placenta, syncytin-1 and 2, encoded by ERVWE1 and ERV-FRD proviral loci, respectively. These fusogenic Envs contribute to the differentiation of multinucleated syncytiotrophoblast in placental chorionic villi. In non-placental tissues, however, expression of these fusogenic proteins has to be suppressed because of high risk for tissue integrity and cancer development. We have previously shown that the 5' long terminal repeat, the regulatory region of syncytin-1 is epigenetically suppressed by DNA methylation in non-placental tissues.