Integrated regulation of class II human endogenous retroviruses in a breast cancer cell line

Abstract

Endogenous retroviruses (ERVs) are still regarded as foreign invaders by most biologists. Because of structural and positional homology of ERVs in human and ape genomes, they have been considered molecular evidences of common ancestry. Using a breast cancer cell line, we analyzed the regulatory features of a group of human endogenous retroviruses (HERV-K), and found that they contain multiple sequence motifs subjecting them to regulation by sex hormones, a stem cell-specific transcription factor (OCT4), and DNA methylation. Mutation of the OCT4 motif abrogates their response to sex hormones, while methylation of a progesterone-response element enhances receptor-binding. We also found that solo LTRs of HERVK enable hormonal regulation of downstream cellular genes. The findings support the hypothesis that ERVs are integral parts of eukaryotic genomes and are designed to regulate interspersed genes, especially in reproduction and development.