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Transcription factor family-specific DNA shape readout revealed by quantitative specificity models
Lin Yang1, Yaron Orenstein2, Arttu Jolma3
1Molecular and Computational Biology Program, Departments of Biological Sciences, Chemistry, Physics & Astronomy, and Computer Science, University of Southern California, Los Angeles, CA, USA.
Molecular Systems Biology
|February 8, 2017
Summary
DNA shape readout is widely used by transcription factors (TFs) for DNA binding specificity, not just a few families. This study reveals TF family-specific shape preferences, offering new insights into TF-DNA interactions.
Area of Science:
- Molecular Biology
- Genomics
- Bioinformatics
Background:
- Transcription factors (TFs) bind DNA via base readout and DNA shape readout.
- The extent of DNA shape readout utilization across TF families is largely unknown.
Purpose of the Study:
- To investigate the prevalence and importance of DNA shape readout in mammalian transcription factor families.
- To characterize TF family-specific DNA shape preferences and their positional dependence.
Main Methods:
- Analysis of resequenced high-throughput SELEX (HT-SELEX) data from mammalian TFs.
- Application of statistical machine learning and feature selection techniques.
- Development of novel DNA shape logos for visualization.
Main Results:
- DNA shape readout is a significant mechanism across diverse TF families, particularly in flanking regions of binding sites.
- Identified nucleotide position-dependent DNA shape readout.
- Demonstrated TF family-specific variations in shape readout preferences.
Conclusions:
- DNA shape readout is extensively utilized by most TF families, contributing to DNA-binding specificity.
- Novel DNA shape logos provide a new method for visualizing TF-DNA shape preferences.
- Mechanistic insights into TF-DNA binding can be gained without atomic-resolution structures.
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