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

• Published in: International journal of molecular sciences Vol. 19; no. 12; p. 3865
• Main Authors: Moosa, Mahdi Muhammad, Tsoi, Phoebe S, Choi, Kyoung-Jae, Ferreon, Allan Chris M, Ferreon, Josephine C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04.12.2018; MDPI
• Subjects: Anisotropy; Binding sites; Cell fate; Communication; Deoxyribonucleic acid; DNA; DNA conformational landscape; DNA-protein interactions; Experiments; Fluorescence; Fluorescence spectroscopy; Functional plasticity; Functionals; Histograms; Microscopy; Population; sequential DNA bending; smFRET; Sox2 sequential DNA loading; transcription factor dosage; Transcription factors; transcription factors; DNA-protein interactions; DNA conformational landscape; smFRET; Sox2 sequential DNA loading; transcription factor dosage; sequential DNA bending
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19123865

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.