TF-MAPS: fast high-resolution functional and allosteric mapping of DNA-binding proteins.

TF-MAPs maps distance-dependent, anisotropic allostery in three human disease transcription factors—HNF1A, FOXG1, and FOXP1—linking the DNA-binding interface to protein surface features.

• Why it matters: Most transcription factors lack known allosteric ligands or sites, and their DNA-binding interfaces are large, limiting mechanistic interpretation of variants and therapeutic modulation.
• What they did: The study introduces TF-MAPs, a scalable platform for functional and allosteric mapping of sequence-specific DNA-binding proteins, and applies it to HNF1A, FOXG1, and FOXP1.
• The result: FOXG1 and FOXP1 show diverged allosteric surfaces, and all three proteins contain small pockets where mutations affect DNA binding, enabling mechanistic variant interpretation and guiding TF-modulating therapeutic development.

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