FoxO1 and HNF1α cooperatively remodel nucleosome architecture and mechanical stability to activate transcription
- 1UC Berkeley
Abstract
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 HNF1 binds SHL +5/+7 as a dimer, induces extensive DNA unwrapping without perturbing the histone core, and reshapes nucleosome disassembly dynamics. FoxO1 enhances HNF1 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 HNF1 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 HNF1 recruitment, and together they remodel nucleosome architecture both in vitro and in native chromatin.
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BibTeX
@misc{ariza2026foxo1,
title = {{FoxO1 and HNF1α cooperatively remodel nucleosome architecture and mechanical stability to activate transcription}},
author = {A. J. Florez Ariza and Z. Yang and R. P. Sosa and C. Diaz-Cellis and H. J. Richter and V. Ramani and C. J. Bustamante and E. Nogales},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.01.763477},
url = {https://www.biorxiv.org/content/10.64898/2026.11.01.763477v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - FoxO1 and HNF1α cooperatively remodel nucleosome architecture and mechanical stability to activate transcription
AU - A. J. Florez Ariza
AU - Z. Yang
AU - R. P. Sosa
AU - C. Diaz-Cellis
AU - H. J. Richter
AU - V. Ramani
AU - C. J. Bustamante
AU - E. Nogales
PY - 2026
DA - 2026/11/01
PB - bioRxiv
DO - 10.64898/2026.11.01.763477
UR - https://www.biorxiv.org/content/10.64898/2026.11.01.763477v1
AB - 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 HNF1 binds SHL +5/+7 as a dimer, induces extensive DNA unwrapping without perturbing the histone core, and reshapes nucleosome disassembly dynamics. FoxO1 enhances HNF1 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 HNF1 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 HNF1 recruitment, and together they remodel nucleosome architecture both in vitro and in native chromatin.
ER -