Transposable elements as a potent source of diverse cis-regulatory sequences in mammalian genomes

Eukaryotic gene regulation is mediated by cis-regulatory elements, which are embedded within the vast non-coding genomic space and recognized by the transcription factors in a sequence- and context-dependent manner. A large proportion of eukaryotic genomes, including at least half of the human genome, are composed of transposable elements (TEs)

Transcription factors (TF) are proteins that regulate gene expression by binding to DNA at specific sequence motifs.

differences across species are thought to be largely driven by changes in gene expression, mediated by divergence in cis-regulatory elements [106,107]. Recent progress in the field revealed that a substantial portion of mammalian cis-regulatory sequences is derived from TEs. These TE-derived cis-regulatory elements are often cell type- and species/clade-specific and can contribute to gene expression regulation through many diverse mechanisms

The prevalence of TE utilization for regulatory functions may differ between cell types and developmental stages. Indeed, TEs seem to play an outsized role during mammalian pre- and peri-implantation development, where whole subclasses of TEs (such as MERVL in mice, or HERV-K and HERV-H in humans) function in host gene regulation as alternative promoters, enhancers or boundary elements. This widespread utilization of TEs during early development is likely facilitated both by the global epigenomic de-repression during this time of embryogenesis and by the fact that to successfully propagate through vertical transmission

Since we have only begun to systematically assess the function of TEs in gene control, it is likely that we are still vastly underestimating their impact as well as the diversity of mechanisms by which TEs can influence transcription, post-transcriptional gene regulation, genome organization

our understanding of TEs has come a long way from the notion of ‘junk’ DNA. What persists is Barbara McClintock’s early vision of TEs as ‘controlling elements’