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. 1993 Sep;13(9):5794–5804. doi: 10.1128/mcb.13.9.5794

The orphan receptors NGFI-B and steroidogenic factor 1 establish monomer binding as a third paradigm of nuclear receptor-DNA interaction.

T E Wilson 1, T J Fahrner 1, J Milbrandt 1
PMCID: PMC360322  PMID: 8395013

Abstract

We examined in detail the DNA interaction of the nuclear receptors NGFI-B and steroidogenic factor 1 (SF-1) by using a series of gain-of-function domain swaps. NGFI-B bound with high affinity as a monomer to a nearly linear DNA molecule. The prototypic zinc modules interacted with a half-site of the estrogen receptor class, and a distinct protein motif carboxy terminal to the zinc modules (the A box) interacted with two A/T base pairs 5' to the half-site. SF-1 bound in the same manner as NGFI-B, with an overlapping but distinct sequence requirement 5' to the half-site. The key features that distinguished the NGFI-B and SF-1 interactions were an amino group in the minor groove of the SF-1 binding sequence and an asparagine in the SF-1 A box. These results define a common mechanism of NGFI-B and SF-1 DNA binding, which may underlie a competitive mechanism of gene regulation in steroidogenic tissues that express these proteins. This monomer-DNA interaction represents a third paradigm of DNA binding by nuclear receptors in addition to direct and inverted dimerization.

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