Modulation of DNA rheology by a transcription factor that forms aging microgels
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arXiv
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| Auteurs principaux: | , , , , , , |
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| Format: | Preprint |
| Publié: |
2025
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| _version_ | 1866917119360237568 |
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| author | Hong-Minh, Amandine Fosado, Yair Augusto Gutiérrez Guild, Abbie Mullin, Nicholas Spagnolo, Laura Chambers, Ian Michieletto, Davide |
| author_facet | Hong-Minh, Amandine Fosado, Yair Augusto Gutiérrez Guild, Abbie Mullin, Nicholas Spagnolo, Laura Chambers, Ian Michieletto, Davide |
| contents | Proteins and nucleic acids form non-Newtonian liquids with complex rheological properties that contribute to their function in vivo. Here we investigate the rheology of the transcription factor NANOG, a key protein in sustaining embryonic stem cell self-renewal. We discover that at high concentrations NANOG forms macroscopic aging gels through its intrinsically disordered tryptophan-rich domain. By combining molecular dynamics simulations, mass photometry and Cryo-EM, we also discover that NANOG forms self-limiting micelle-like clusters which expose their DNA-binding domains. In dense solutions of DNA, NANOG micelle-like structures stabilize intermolecular entanglements and crosslinks, forming microgel-like structures. Our findings suggest that NANOG may contribute to regulate gene expression in a unconventional way: by restricting and stabilizing genome dynamics at key transcriptional sites through the formation of an aging microgel-like structure, potentially enabling mechanical memory in the gene network. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2512_02864 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Modulation of DNA rheology by a transcription factor that forms aging microgels Hong-Minh, Amandine Fosado, Yair Augusto Gutiérrez Guild, Abbie Mullin, Nicholas Spagnolo, Laura Chambers, Ian Michieletto, Davide Soft Condensed Matter Other Condensed Matter Biological Physics Computational Physics Biomolecules Proteins and nucleic acids form non-Newtonian liquids with complex rheological properties that contribute to their function in vivo. Here we investigate the rheology of the transcription factor NANOG, a key protein in sustaining embryonic stem cell self-renewal. We discover that at high concentrations NANOG forms macroscopic aging gels through its intrinsically disordered tryptophan-rich domain. By combining molecular dynamics simulations, mass photometry and Cryo-EM, we also discover that NANOG forms self-limiting micelle-like clusters which expose their DNA-binding domains. In dense solutions of DNA, NANOG micelle-like structures stabilize intermolecular entanglements and crosslinks, forming microgel-like structures. Our findings suggest that NANOG may contribute to regulate gene expression in a unconventional way: by restricting and stabilizing genome dynamics at key transcriptional sites through the formation of an aging microgel-like structure, potentially enabling mechanical memory in the gene network. |
| title | Modulation of DNA rheology by a transcription factor that forms aging microgels |
| topic | Soft Condensed Matter Other Condensed Matter Biological Physics Computational Physics Biomolecules |
| url | https://arxiv.org/abs/2512.02864 |