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Updated: Jul 3, 2025

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
Published on: February 7, 2019
Predicting the DNA binding specificity of transcription factor mutants using family-level biophysically interpretable
Shaoxun Liu1, Pilar Gomez-Alcala1, Christ Leemans1
1Department of Biological Sciences, Columbia University, New York, NY, USA.
This study introduces a novel method to predict how mutations in transcription factors (TFs) alter their DNA binding preferences. This approach accurately forecasts changes in binding free energy for TF mutants, aiding disease mutation impact analysis.
Area of Science:
- Molecular Biology
- Genomics
- Bioinformatics
Background:
- Transcription factors (TFs) regulate cellular processes through sequence-specific DNA binding.
- High-throughput assays and machine learning define TF molecular recognition and sequence preferences.
- Disease-associated mutations in TF DNA binding domains can alter these preferences.
Conclusions:
- The developed method accurately predicts mutation-induced changes in TF sequence specificity.
- This approach offers a powerful tool for understanding disease mechanisms related to TF mutations.
- Enables biophysically interpretable predictions of TF-DNA interactions.
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