In addition to signaling directly through EREs, ER can act more as a coactivator to modulate transcriptional responses via interactions with other classes of DNA-bound transcription factors, such as AP-1 or SP-1 [ 13, 14].
Disruption of both EREs abrogated ER binding and nearly abolished p53 binding to the p53 RE-T region, consistent with the results of the functional assays.
The ERE-bound ER recruits an ensemble of co-factors responsible for the alteration of local chromatin structure and interaction with the basal transcription machinery.
Interestingly, this effect was primarily observed at a low concentration of 4-OH-TAM (10 nM) and was associated with mild ERE-mediated ER transcriptional activity.
Only the short form of ERR β is expressed in breast tissue (Zhou et al, 2006), and these isoforms also differ in tissue specificity, intracellular localisation and the modulation of ERE-dependent ER α transcriptional activity (Yu et al, 2008).
Interestingly, 10 nM 4-OH-TAM provided a mild promitogenic effect, increasing IGF-1-dependent proliferation (17% to 27%; P < 0.05) and ERE-mediated ER transcriptional activity in MCF7/IGF-1R cells (P < 0.05), whereas it remained inhibitory in parental MCF7 cells (15%to20%0%; P < 0.05).
NFκB activation modulates ERE activity by an ER and NFκB dependent mechanism and can enhance ER-mediated endogenous gene expression in an in-vitro human endometrial epithelial cell model.
Meerts et al. (2001) tested 17 PBDE congeners for estrogenic activity in an ERE-luciferase assay (ER-CALUX; Legler et al. 1999).
Among the 107 gene sets associated with luminal A tumours, 38 (35.5%) were related to genes containing EREs or to ER-associated transcription factors whereas none of these gene sets was related to E2F1 transcription factor (Fig 5G).
In particular, Carlsson et al. (1995) [ 27] reported 20-fold lower association rate constant of the hormone-receptor complex to ERE at low concentrations of ER, when the predominant form of ER is a monomer, as compared to higher concentrations (ER > 12 nM), when the majority of ER present as homodimers.
Additionally, because Ad-ERE-GFP uses only ERE as readout of ER-driven transcriptional activity, it is more specific than PgR, which is influenced by many transcriptional cofactors.
