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Int J Mol Sci. 2018 Dec 4;19(12). pii: E3865. doi: 10.3390/ijms19123865.

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

Author information

1
Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA. Mahdi.Moosa@bcm.edu.
2
Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA. Phoebe.Tsoi@bcm.edu.
3
Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA. Kyoungjae.Choi@bcm.edu.
4
Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA. Allan.Ferreon@bcm.edu.
5
Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA. Josephine.Ferreon@bcm.edu.

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:

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

PMID:
30518054
PMCID:
PMC6321608
DOI:
10.3390/ijms19123865
[Indexed for MEDLINE]
Free PMC Article

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