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bioRxiv · 10.1101/634386

Nucleosomal DNA dynamics mediate Oct4 pioneer factor binding

Huertas, J.·MacCarthy, C. M.·Schoeler, H. R.·Cojocaru, V.
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Abstract

Transcription factor (TF) proteins bind to DNA to regulate gene expression. Normally, accessibility to DNA is required for their function. However, in the nucleus the DNA is often inaccessible, wrapped around histone proteins in nucleosomes forming the chromatin. Pioneer TFs are thought to induce chromatin opening by recognizing their DNA binding sites on nucleosomes. For example, Oct4, a master regulator and inducer of stem cell pluripotency, binds to DNA in nucleosomes in a sequence specific manner. Here we reveal the structural dynamics of nucleosomes that mediate Oct4 binding. Nucleosome mobility and the amplitude of nucleosome motions such as breathing and twisting correlate with the number of Oct4 binding sites available. Moreover, the regions around the binding sites display higher local mobility. Probing different structures of Oct4-nucleosome complexes, we show that alternative configurations display stable protein-DNA interactions and are compatible with the DNA curvature and DNA-histone interactions.

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Huertas, J., MacCarthy, C. M., Schoeler, H. R., Cojocaru, V.. 2019-05-10. Nucleosomal DNA dynamics mediate Oct4 pioneer factor binding. https://doi.org/10.1101/634386

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