Besides, a number of other putative cis-elements such as ERE-like/GCC-box-like and zinc finger binding element-like associated with ERF and ZnF TFs were also more overrepresented in the up-regulated genes albeit being present in both up- and down-regulated genes.
Acting in cooperation with other transcription factors such as Sp1 [34], ERs can also modulate transcription from ½ site EREs.
The possibility exists that many of these genes are transcriptionally regulated by non-ERE mediated mechanisms such as those involving ER binding to the AP1 or SP1 transcription factors [ 33].
The perfect consensus sequence of ERE is GGTCAnnnTGACC, however, all EREs in MTO1 strikingly appeared as perfect or imperfect half-ERE (hERE) rather than a full ERE such as GGTCA, TGACC, GGCCA, and GGCAC.
This result indicated the potential involvement of transcriptional regulators other than ERE, such as AP-1 and Sp1, in E2-regulated gene expression [24], [25].
MAPK and Akt have been shown to phosphorylate the estrogen receptor (ER) at Ser-118 and Ser-167, respectively, thereby mimicking the effects of estrogenic activity such as estrogen responsive element (ERE -dependent transcription.
Our analysis confirms important characteristics of EREs such as their intergenic localization, the presence of cofactor sites, and GC biased local nucleotide composition.
It was also shown that some hERα targets, such as c-Myc, lack the ERE, but instead contain AP1 or SP1 binding sites, which appear to be essential for transcription in vitro [ 5, 8, 9].
ERa regulates gene expression either by binding to estrogen response elements (ERE) or through ERE-independent signaling (such as interactions with other transcription factors like AP-1, SP1, NF-KB) [ 20- 24].
Furthermore, we noticed a moderate enrichment of other ERE like-elements such as JA response element-like elements among the up-regulated genes (Table 1).
