Let’s explore how various Estrogen Response Element (ERE) sequences affect how Estrogen Receptors (ERS) bind to them and how this interaction influences the activation of gene transcription. Various detection methods have been utilized across different studies to achieve this.
INFLUENCE OF NATURALLY OCCURRING ERES ON TRANSCRIPTIONAL ACTIVATION AND ER BINDING:
Studies of naturally occurring ERES have revealed a direct correlation between the ER’s binding affinity to an ERE and its ability to activate transcription. This observation holds for both ER subtypes, ERa and ERB.
IMPACT OF MUTATIONS IN ERES SEQUENCE ON TRANSCRIPTIONAL ACTIVATION AND ER BINDING:
Mutations in the consensus sequence (the most common sequence pattern) of ERES tend to reduce their ability to activate transcription and weaken their binding with Estrogen Receptors (ERS). This suggests that the specific sequence of the ERE plays a crucial role in determining both its affinity for the ER and its potency to activate transcription.
AFFINITY OF ERα AND ERB for ERES SEQUENCES:
Further research has demonstrated that ERa and ERẞ bind to the same ERES sequences. However, ERa displays approximately twofold higher affinity for ERES compared to ERB. This suggests that the two ER subtypes may have distinct roles in regulating gene expression in response to estrogen.
DIFFERENTIAL TRANSCRIPTIONAL ACTIVATION INDUCED BY VARIOUS ERES:
In a particular study comparing different ERES (from African clawed frog (Xenopus laevis) vitellogenin A2 and B1 genes, human pS2 gene, and gene encoding oxytocin), researchers conducted co-transfection experiments in HeLa cells. They used a chloramphenicol acetyltransferase assay to measure the level of transcriptional activation induced by these different ERES. The results showed that the vitellogenin A2 ERE induced the strongest transcriptional activation (10.5-fold), followed by the oxytocin ERE (9.5-fold), the PS2 ERE (2.7-fold), and the vitellogenin B1 ERE (1.6-fold). Essentially, this means that various ERES have different strengths in their ability to activate gene transcription upon binding with ERs.
