Nucleosome-bound SOX2 and SOX11 structures elucidate pioneer factor function.

Area of Science:

• Molecular Biology
• Epigenetics
• Structural Biology

Background:

• Pioneer transcription factors are essential for cellular processes including pluripotency, differentiation, and reprogramming.
• These factors can access and regulate genes within tightly packed chromatin.
• SOX2 is a key pioneer factor critical for embryonic stem cell pluripotency and self-renewal.

Purpose of the Study:

• To elucidate the structural mechanisms by which SOX2 and SOX11 pioneer transcription factors interact with nucleosomes.
• To understand how these factors facilitate chromatin accessibility for gene regulation.

Main Methods:

• Cryo-electron microscopy was used to determine the structures of SOX2 and SOX11 DNA-binding domains bound to nucleosomes.
• Analysis focused on the molecular interactions and conformational changes induced upon SOX factor binding.

Main Results:

• SOX factors bind to DNA at superhelical location 2 on the nucleosome, causing local DNA distortion.
• Binding facilitates the detachment of DNA ends from the histone octamer, enhancing DNA accessibility.
• SOX binding can reposition the histone H4 N-terminal tail, potentially disrupting higher-order nucleosome stacking.

Conclusions:

• Pioneer transcription factors utilize binding energy to initiate chromatin opening.
• This process involves nucleosome remodeling and facilitates subsequent gene transcription.
• The findings provide structural insights into how pioneer factors overcome chromatin barriers to regulate gene expression.