Factors regulating endogenous retroviral sequences in human and mouse

Endogenous retroviruses ( ERVs) are stably integrated in the genome of vertebrates and inherited as Mendelian genes. The several human ERV ( HERV) families and related elements represent up to 5 - 8% of the DNA of our species. ERVs may be involved in the regulation of adjacent genomic loci, especially promoting the tissue-specific expression of genes; some HERVs may have functional roles, e. g., coding for the placental fusogenic protein, syncytin. This paper reviews the growing evidence about factors that may modulate ERVs, including: cell and tissue types ( with special attention to placenta and germ cells), processes related to differentiation and aging, cytokines, agents that disrupt cell functions ( e. g., DNA hypomethylating agents) and steroids. Special attention is given to HERVs, due to their possible involvement in autoimmunity and reproduction, as well as altered expression in some cancer types; moreover, different HERV families may deserve specific attention, due to remarkable differences concerning, e. g., expression in tissues. A comparison with factors interacting with murine ERV-related sequences indicates that the mouse may be a useful model for studying some patterns of HERV regulation. Overall, the available evidence identifies the diverse, potential interactions with endogenous or exogenous factors as a promising field for investigating the roles of ERVs in physiology and disease. Copyright (C) 2004 S. Karger AG, Basel.