FoxO1 and HNF1α cooperatively remodel nucleosome architecture and mechanical stability to activate transcription

FoxO1 binding at SHL +2 on human IGFBP1 promoter nucleosomes reduces nucleosome mechanical stability and destabilizes the histone core, enabling enhanced distal DNA unwrapping.

• Why it matters: TF cooperation on nucleosomal DNA targets is not well understood, especially how pioneer and partner factors coordinate nucleosome architecture and mechanics to activate transcription.
• What they did: Using cryo-EM and force spectroscopy, they compared FoxO1 at SHL +2 with HNF1 at SHL +5/+7, then tested recruitment and in-cell nucleosome footprinting on active promoters.
• The result: FoxO1 enhances HNF1 recruitment, and together they stabilize nucleosomes during mechanically induced disassembly, yielding an intermediate nucleosome phenotype with increased unwrapped/subnucleosomes versus stabilized/breathing nucleosomes.

AI summary of the abstract · may contain errors · not medical advice · read the paper.