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Title:Role of Dimerization in Binding of Estrogen Receptor to the Estrogen Response Element
Author(s):Kuntz, Martin Andrew, III
Doctoral Committee Chair(s):Shapiro, David J.
Department / Program:Biochemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Chemistry, Biochemistry
Abstract:I investigated the role of dimerization in the binding of estrogen receptor to estrogen response elements. I found that the affinity of the estrogen receptor for the consensus estrogen response element is increased by six- to ten-fold by dimerization. This observation was true for both full length estrogen receptor or for the isolated DNA binding domain which was artificially dimerized with either an antibody or a peptide linker. The increase in affinity for nonconsensus estrogen response elements with a single mutated half-site due to dimerization was much larger. Since elements of this type are the vast majority found in naturally occurring genes, dimerization is essential for physiological functioning of the estrogen receptor. Kinetics studies of estrogen receptor constructs interacting with the consensus ERE demonstrated that an increase in stability of the bound complex was the primary effect of dimerization. This observation supports a sequential mechanism of the estrogen receptor DNA binding domains interacting with the estrogen response element. I also determined the affinity of estrogen receptor constructs for widely spaced estrogen response element half-sites to be reduced by approximately three-fold compared to the consensus estrogen response element. This indicates a weak interaction between DNA binding domains when bound to the consensus estrogen response element. A full length estrogen receptor which was incapable of dimerization via its hormone binding domain was found to display wild-type ability to activate transcription in transient transfection assays and several potential mechanisms are proposed to account for this observation.
Issue Date:1999
Description:150 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1999.
Other Identifier(s):(MiAaPQ)AAI9921707
Date Available in IDEALS:2015-09-25
Date Deposited:1999

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