Direct Single-Molecule Observation of Sequential DNA Bending Transitions by the Sox2 HMG Box

Abstract

Sox2 is a pioneer transcription factor that initiates cell fate reprogramming through locus-specific differential regulation. Mechanistically, it was assumed that Sox2 achieves its regulatory diversity via heterodimerization with partner transcription factors. Here, utilizing single-molecule fluorescence spectroscopy, we show that Sox2 alone can modulate DNA structural landscape in a dosage-dependent manner. We propose that such stoichiometric tuning of regulatory DNAs is crucial to the diverse biological functions of Sox2, and represents a generic mechanism of conferring functional plasticity and multiplicity to transcription factors.

Keywords

• transcription factors
• DNA-protein interactions
• Sox2 sequential DNA loading
• smFRET
• DNA conformational landscape
• sequential DNA bending
• transcription factor dosage