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Transcription factors ERα and Sox2 have differing multiphasic DNA and RNA binding mechanisms
Wayne O Hemphill1,2, Halley R Steiner1, Jackson R Kominsky1,2
1Department of Biochemistry, University of Colorado Boulder, Boulder, Colorado 80303 USA.
Biorxiv : the Preprint Server for Biology
|April 2, 2024
Summary
Transcription factors (TFs) like ERα and Sox2 bind RNA and DNA with complex, multiphasic kinetics. ERα exhibits a novel binding mechanism involving sequential association and isomerization.
Area of Science:
- Molecular Biology
- Biophysics
Background:
- Transcription factors (TFs) binding RNA raises questions about mechanisms and regulation.
- Understanding TF-nucleic acid interactions is crucial for gene regulation studies.
Approach:
- Utilized biophysical assays to study DNA and RNA binding kinetics of ERα and Sox2.
- Applied kinetic modeling and simulations to analyze binding behavior.
Key Points:
- Both ERα and Sox2 displayed multiphasic nucleic acid binding kinetics.
- Sox2 binding kinetics align with conventional monomer association/dissociation models.
- ERα exhibited unique triphasic association and biphasic dissociation kinetics, suggesting a novel mechanism.
Conclusions:
- ERα and Sox2 possess complex, previously unappreciated nucleic acid binding kinetics.
- ERα employs a novel reaction mechanism for nucleic acid binding, distinct from Sox2.
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