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J Biol Chem, Vol. 273, Issue 45, 29321-29330, November 6, 1998
From the Department of Biochemistry and Biophysics and the
University of Rochester Cancer Center, The University of Rochester
School of Medicine and Dentistry, Rochester, New York 14642
The estrogen receptor (ER) is a transcription
factor that binds to a specific DNA sequence found in the regulatory
regions of estrogen-responsive genes, called the estrogen response
element (ERE). Many genes that contain EREs have been identified, and most of these EREs contain one or more changes from the core consensus sequence, a 13-nucleotide segment with 10 nucleotides forming an
inverted repeat. A number of genes have multiple copies of these
imperfect EREs. In order to understand why natural EREs have developed
in this manner, we have attempted to define the basic sequence
requirements for ER binding. To this end, we measured the binding of
homodimeric ER to a variety of nonconsensus EREs. We discovered that an
ERE containing even a single change from the consensus may be unable to
bind ER. However, an ERE with two changes from the consensus may be
capable of binding avidly to ER in the context of certain flanking
sequences. We found that changes in the sequences flanking a
nonconsensus ERE can greatly alter ER-ERE affinity, either positively
or negatively. Careful study of sequences flanking a series of EREs
made it possible to develop rules that predict whether ER binds to a
given natural ERE and also to predict the relative amounts of binding
when comparing two EREs.
Sequence Requirements for Estrogen Receptor Binding to Estrogen
Response Elements
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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