Abstract
Estrogen receptors (ERs) efficiently potentiate the transcriptional activity of prolactin-activated Stat5b through a mechanism that involves the ER DNA-binding domain (DBD) and the hinge domain. We have identified residues within the DBD of ER that are critical for the functional interaction of ER with Stat5b. We show that disruption of the second zinc finger structure abrogated cross-talk between ER and Stat5b, while the structure of the first zinc finger was not important. Furthermore, we confirm that intact DNA binding activity was not required for potentiation of Stat5b activity and that the dimerization of ER did not seem to be involved. Ligand-bound ERs also modulated activating protein 1-dependent transcription, and our data demonstrate that both zinc finger structures of the ER DBD are important for an intact response. We show that introduction of various point mutations within the DBD altered the response of the receptor to 17beta-estradiol and to the estrogen antagonists 4-hydroxytamoxifen and ICI 182,870 on the collagenase promoter. These findings provide new insights into the mechanisms by which ERs act in cross-talk with non-related transcription factors.
Highlights
The Estrogen receptors (ERs) is able to regulate gene expression in the absence of DNA binding by modulating the activities of other transcription factors
We demonstrated that ER␣ and ER can interact with Stat5 through the DNA-binding domain (DBD)/hinge domain, and we showed that the interaction of ER with classical co-activator proteins is dispensable for the potentiation of Stat5 activity
We show that specific residues within the second helical structure of the ER DBD are essential for the potentiation of Stat5b transcriptional activity, whereas intact DNA binding activity per se is not required
Summary
The ER is able to regulate gene expression in the absence of DNA binding by modulating the activities of other transcription factors. Mutations within the Second Helical Structure of ER DBD Disrupt Functional Interaction with Stat5b—We have previously reported that ER-mediated potentiation of Stat5b transcriptional activity through cross-talk in the nucleus requires the DBD/hinge domain [7].
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