Endogenous retroviruses (ERVs) arise from germline invasion of their exogenous counterparts. Once integrated, ERVs can be inherited to subsequent generations. With potentially pathogenic effects, ERVs are generally repressed by their hosts through epigenetic mechanisms, including DNA methylation and histone modifications. However, throughout evolution, a portion of ERV elements have been coopted to exert particular functions for the host genome, as coding genes and cis-regulatory elements. As previously reported, several ERV families exhibit stage-specific activity in human embryonic development, of which LTR12C was one family showing tissue-specific activity. In most genomic studies, repetitive elements are often excluded, due to the technical difficulty of accurate mapping; hence, the...[ Read more ]

Endogenous retroviruses (ERVs) arise from germline invasion of their exogenous counterparts. Once integrated, ERVs can be inherited to subsequent generations. With potentially pathogenic effects, ERVs are generally repressed by their hosts through epigenetic mechanisms, including DNA methylation and histone modifications. However, throughout evolution, a portion of ERV elements have been coopted to exert particular functions for the host genome, as coding genes and cis-regulatory elements. As previously reported, several ERV families exhibit stage-specific activity in human embryonic development, of which LTR12C was one family showing tissue-specific activity. In most genomic studies, repetitive elements are often excluded, due to the technical difficulty of accurate mapping; hence, the scope of this phenomenon remains unclear. In this study, we aim to delineate cis-regulatory functions of ERVs through a combination of bioinformatic analyses and molecular epigenetic approaches. We developed a new technique to facilitate better identify the epigenetic status of repetitive sequences known as ChIP assisted repeat pinpointing (CARP-seq). Moreover, we selected several embryonic stem cells (ESC)-specific LTR12C elements to study their epigenetic states and functions. Taken together, we attempt to elucidate the contribution of ERVs in the cis-regulatory network of human ESCs.