The High Mobility Group Protein 1 Enhances Binding of the Estrogen Receptor DNA Binding Domain to the Estrogen Response Element

• Published in: Molecular endocrinology (Baltimore, Md.) Vol. 12; no. 5; pp. 664 - 674
• Main Authors: Romine, Lorene E, Wood, Jennifer R, Lamia, LuAnne A, Prendergast, Paul, Edwards, Dean P, Nardulli, Ann M
• Format: Journal Article
• Language: English
• Published: Endocrine Society 01-05-1998; Oxford University Press
• ISSN: 0888-8809; 1944-9917
• DOI: 10.1210/mend.12.5.0111

We have examined the ability of the high-mobility
group protein 1 (HMG1) to alter binding of the estrogen receptor
DNA-binding domain (DBD) to the estrogen response element (ERE). HMG1
dramatically enhanced binding of purified, bacterially expressed DBD to
the consensus vitellogenin A2 ERE in a dose-dependent manner. The
ability of HMG1 to stabilize the DBD-ERE complex resulted in part from
a decrease in the dissociation rate of the DBD from the ERE. Antibody
supershift experiments demonstrated that HMG1 was also capable of
forming a ternary complex with the ERE-bound DBD in the presence of
HMG1-specific antibody. HMG1 did not substantially affect DBD-ERE
contacts as assessed by methylation interference assays, nor did it
alter the ability of the DBD to induce distortion in ERE-containing DNA
fragments. Because HMG1 dramatically enhanced estrogen receptor DBD
binding to the ERE, and the DBD is the most highly conserved region
among the nuclear receptor superfamily members, HMG1 may function to
enhance binding of other nuclear receptors to their respective response
elements and act in concert with coactivator proteins to regulate
expression of hormone-responsive genes.