Molecular Mechanism of Nucleosome Recognition by the Pioneer Transcription Factor Sox

Ozden B., Boopathi R., Barlas A. B., Lone I. N., Bednar J., Petosa C., ...Daha Fazla

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1021/acs.jcim.2c01520
  • Dergi Adı: JOURNAL OF CHEMICAL INFORMATION AND MODELING
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, Compendex, Computer & Applied Sciences, MEDLINE
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Pioneer transcription factors (PTFs) have the remarkableabilityto directly bind to chromatin to stimulate vital cellular processes.In this work, we dissect the universal binding mode of Sox PTF bycombining extensive molecular simulations and physiochemistry approaches,along with DNA footprinting techniques. As a result, we show thatwhen Sox consensus DNA is located at the solvent-facing DNA strand,Sox binds to the compact nucleosome without imposing any significantconformational changes. We also reveal that the base-specific Sox:DNAinteractions (base reading) and Sox-induced DNA changes (shape reading)are concurrently required for sequence-specific nucleosomal DNA recognition.Among three different nucleosome positions located on the positiveDNA arm, a sequence-specific reading mechanism is solely satisfiedat the superhelical location 2 (SHL2). While SHL2 acts transparentlyfor solvent-facing Sox binding, among the other two positions, SHL4permits only shape reading. The final position, SHL0 (dyad), on theother hand, allows no reading mechanism. These findings demonstratethat Sox-based nucleosome recognition is essentially guided by intrinsicnucleosome properties, permitting varying degrees of DNA recognition.