ETS-related gene response element (ERG-RE)

The ETS-related gene (ERG) response element consists of specific double-stranded DNA sequences, typically containing a conserved 5'-GGAA/T-3' core motif, that serve as the primary docking sites for the ERG transcription factor (Sizemore et al., 2017). In healthy physiological states, ERG binds to these motifs to regulate genes essential for vascular development, angiogenesis, and hematopoiesis. However, in approximately 50% of prostate cancer cases, a chromosomal translocation creates the TMPRSS2-ERG fusion, resulting in the massive overexpression of ERG (Tomlins et al., 2005). This leads to the aberrant activation of oncogenic pathways as ERG binds to its response elements to drive cell invasion and epithelial-mesenchymal transition. Because transcription factors are traditionally difficult to target with small molecules, therapeutic strategies have shifted toward the DNA motif itself. These include the use of decoy oligonucleotides that mimic the response element to sequester ERG protein and small molecules like DB1255 that bind the DNA minor groove at these specific sites to competitively inhibit ERG recruitment (Nhili et al., 2013).

Other names

ERG binding siteETS binding siteERG-binding DNA motifERG-responsive elementEBS

Competitive inhibition of transcription factor binding via DNA minor groove binding or decoy sequestration.