Role of Dimerization in Binding of Estrogen Receptor to the Estrogen Response Element
Kuntz, Martin Andrew, III
This item is only available for download by members of the University of Illinois community. Students, faculty, and staff at the U of I may log in with your NetID and password to view the item. If you are trying to access an Illinois-restricted dissertation or thesis, you can request a copy through your library's Inter-Library Loan office or purchase a copy directly from ProQuest.
Permalink
https://hdl.handle.net/2142/84901
Description
Title
Role of Dimerization in Binding of Estrogen Receptor to the Estrogen Response Element
Author(s)
Kuntz, Martin Andrew, III
Issue Date
1999
Doctoral Committee Chair(s)
Shapiro, David J.
Department of Study
Biochemistry
Discipline
Biochemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Biochemistry
Language
eng
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.
Use this login method if you
don't
have an
@illinois.edu
email address.
(Oops, I do have one)
IDEALS migrated to a new platform on June 23, 2022. If you created
your account prior to this date, you will have to reset your password
using the forgot-password link below.
