In the regulatory area of estrogen-targeted genes, multiple sequences resembling estrogen receptor elements (ERES) are commonly observed. This observation has given rise to the idea of the estrogen response unit (ERU). An ERU consists of imperfectly matched palindromic elements or even half-elements and they might be quite far apart from each other on the DNA strand, sometimes separated by hundreds of base pairs. This adds another layer of complexity to the regulation of gene expression by estrogen.
MECHANISMS BEHIND TRANSCRIPTIONAL SYNERGISM IN ESTROGEN RESPONSE UNITS (ERUS):
The activation of gene transcription by estrogen occurs through the combined action of multiple elements within an Estrogen Response Unit (ERU). Research has shown that this transcriptional synergy happens when the Estrogen Receptor (ER) attaches to these distinct elements, leading to enhanced gene expression. This has been observed in both natural ERUS like the Xenopus laevis vitellogenin B1 ERU, as well as in artificially created ones. Although the exact mechanism behind this transcriptional synergism isn’t fully understood, several possibilities have been proposed.
- One possibility is that the cooperative recruitment of coactivator proteins by ER dimers bound to different ERES within an ERU enhances transcriptional activation.
- Another hypothesis suggests that direct interactions between ER dimers bound to different ERES within an ERU contribute to the synergistic activation of transcription.
- Additionally, allosteric modulations between the DNA-ER complexes within an ERU could play a role in this process.
