The ligand-mediated nuclear mobility and interaction with estrogen-responsive elements of estrogen receptors are subtype specific.

Abstract:

:17β-Estradiol (E(2)) plays important roles in functions of many tissues. E(2) effects are mediated by estrogen receptor (ER) α and β. ERs regulate transcriptions through estrogen-responsive element (ERE)-dependent and ERE-independent modes of action. ER binding to ERE constitutes the basis of the ERE-dependent pathway. Direct/indirect ER interactions with transcription complexes define ERE-independent signaling. ERs share functional features. Ligand-bound ERs nevertheless induce distinct transcription profiles. Live cell imaging indicates a dynamic nature of gene expressions by highly mobile ERs. However, the relative contribution of ER mobility at the ERE-independent pathway to the overall kinetics of ER mobility remains undefined. We used fluorescent recovery after a photo-bleaching approach to assess the ligand-mediated mobilities of ERE binding-defective ERs, ER(EBD). The decrease in ERα mobility with E(2) or the selective ER modulator 4-hydroxyl-tamoxifen (4HT) was largely due to the interaction of the receptor with ERE. Thus, ERα bound to E(2) or 4HT mediates transcriptions from the ERE-independent pathway with remarkably fast kinetics that contributes fractionally to the overall motility of the receptor. The antagonist Imperial Chemical Industries 182 780 immobilized ERαs. The mobilities of ERβ and ERβ(EBD) in the presence of ligands were indistinguishable kinetically. Thus, ERβ mobility is independent of the nature of ligands and the mode of interaction with target sites. Chimeric ERs indicated that the carboxyl-termini are critical regions for subtype-specific mobility. Therefore, while ERs are highly mobile molecules interacting with target sites with fast kinetics, an indication of the hit-and-run model of transcription, they differ mechanistically to modulate transcriptions.

journal_name

J Mol Endocrinol

authors

Muyan M,Callahan LM,Huang Y,Lee AJ

doi

10.1530/JME-12-0097

subject

Has Abstract

pub_date

2012-10-30 00:00:00

pages

249-66

issue

3

eissn

0952-5041

issn

1479-6813

pii

JME-12-0097

journal_volume

49

pub_type

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