FoxO1 and HNF1α cooperatively remodel nucleosome architecture and mechanical stability to activate transcription
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How different transcription factors (TFs) cooperate to bind nucleosomal DNA targets remains unclear. Cryo-EM and force spectroscopy show that the pioneer factor FoxO1 binds superhelical location (SHL) +2 of nucleosomes assembled on the human IGFBP1 promoter, enhances distal DNA unwrapping, destabilizes the histone core, and reduces nucleosome mechanical stability. TF HNF1α binds SHL +5/+7 as a dimer, induces extensive DNA unwrapping without perturbing the histone core, and reshapes nucleosome disassembly dynamics. FoxO1 enhances HNF1α recruitment, and together they stabilize the nucleosome during its mechanically-induced disassembly trajectories. In-cell nucleosome footprinting on active promoters shows that FoxO1 binding enhances unwrapped nucleosomes and subnucleosomes presence, while HNF1α increases stabilized and “breathing” nucleosomes and reduces the subnucleosome population. Combined, they display an intermediate nucleosome phenotype. Our data leads to a model where FoxO1 destabilizes the nucleosome and enhances HNF1α recruitment, and together they remodel nucleosome architecture both in vitro and in native chromatin.
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FoxO1 and HNF1α cooperatively remodel nucleosome architecture and mechanical stability to activate transcription www.biorxiv.org/content/10.64898/2026.11.01.763477v1 #cryoEM
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The last part of my PhD work is on bioRxiv! Using Cryo-EM, optical tweezers, and in-cell footprinting, we showed that FoxO1 and HNF1α TFs engage and cooperate to bind nucleosomes in vitro and in native chromatin, modulating its architecture and stability. www.biorxiv.org/content/10.6...
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FoxO1 and HNF1α cooperatively remodel nucleosome architecture and mechanical stability to activate transcription https://www.biorxiv.org/content/10.64898/2026.11.01.763477v1
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FoxO1 and HNF1α cooperatively remodel nucleosome architecture and mechanical stability to activate transcription https://www.biorxiv.org/content/10.64898/2026.11.01.763477v1
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