Journal
BIOPHYSICAL JOURNAL
Volume 92, Issue 12, Pages 4415-4423Publisher
CELL PRESS
DOI: 10.1529/biophysj.106.099382
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Estrogen receptors are ligand-activated transcription factors that regulate gene expression by binding to specific DNA sequences. To date, the effect of ligands on the conformation of estrogen receptor alpha (ER alpha)-DNA complex remains a poorly understood issue. In our study, we are introducing the quartz crystal microbalance with dissipation monitoring (QCM-D) as a new alternative to study the conformational differences in protein-DNA complexes. Specifically, we have used QCM-D, in combination with surface plasmon resonance (SPR) spectroscopy, to monitor the binding of ER alpha to a specific DNA (estrogen response element, ERE) and a nonspecific DNA in the presence of either the agonist ligand, 17b-estradiol, the partial antagonist ligand, 4-hydroxytamoxifen, or vehicle alone. Both with presence and absence of ligand, the specific ER alpha-ERE complexes are observed to adopt a more compact conformation compared to nonspecific complexes. This observation is well correlated to the biophysical changes occurring during protein-DNA interaction shown by past structural and mechanism studies. Notably, pretreatment of ERa with E2 and 4OHT affects not only the viscoelasticity and conformation of the protein-DNA complex but also ER alpha binding capacity to immobilized ERE. These results affirm that ligands have remarkable effects on ER alpha-DNA complexes. Understanding these effects will provide insight into how ligand binding promotes subsequent events required for gene transcription.
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