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DNA bending by nuclear receptors

A M Nardulli¹, D J Shapiro

¹Department of Physiology and Biophysics, University of Illinois, Urbana 61801.

Receptor

|January 1, 1993

Summary

Estrogen receptors bend DNA, with stronger bending correlating to more potent transcription activation. This suggests DNA bending is crucial for activating estrogen-responsive genes.

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Area of Science:

Molecular Biology
Genetics
Biochemistry

Background:

Steroid hormone receptors are key ligand-regulated transcription factors, but their transcription activation mechanisms remain unclear.
Transcription factors binding DNA and inducing DNA bending are increasingly recognized.
A functional link between DNA bending and transcription activation is hypothesized.

Purpose of the Study:

To investigate the role of DNA bending in transcription activation by the estrogen receptor.
To quantify DNA bending induced by the estrogen receptor DNA binding domain and the intact estrogen receptor.

Main Methods:

Circular permutation analysis was used to measure DNA bending.
DNA fragments containing estrogen response elements (EREs) were analyzed.
The estrogen receptor DNA binding domain and intact estrogen receptor were tested.

Main Results:

The intact estrogen receptor induced greater DNA bending (56 degrees) than its DNA binding domain (34 degrees).
Higher DNA bending correlated with more potent transcription activation.
Multiple EREs in a DNA fragment resulted in increased DNA bending.

Conclusions:

DNA bending by estrogen receptors appears functionally coupled to transcription activation.
DNA bending may be a critical mechanism in the regulation of estrogen-responsive genes.
These findings advance the understanding of steroid hormone receptor function.

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