The high mobility group protein 1 enhances binding of the estrogen receptor DNA binding domain to the estrogen response element.
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.
Romine
L E
LE
Department of Molecular and Integrative Physiology, University of Illinois, Urbana 61801, USA.
Wood
J R
JR
Lamia
L A
LA
Prendergast
P
P
Edwards
D P
DP
Nardulli
A M
AM
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002417:Cattle; D004247:DNA / Q000378:metabolism; D018983:DNA Footprinting; D053938:DNA Fragmentation; D019281:Dimerization; D004967:Estrogens / Q000235:genetics* / Q000494:pharmacology; D006609:High Mobility Group Proteins / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D011960:Receptors, Estrogen / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000187:drug effects; D014982:Xenopus laevis
D004967:Estrogens; D006609:High Mobility Group Proteins; D011960:Receptors, Estrogen; D004247:DNA