Zooming into Gene Activation: Estrogen Receptor α Dimerization and DNA Binding Visualized by High-Speed Atomic Force Microscopy DOI Creative Commons
Goro Nishide,

Tomoka Ishibashi,

Keesiang Lim

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Estrogen receptor α (ERα) is pivotal in gene regulation, particularly estrogen-responsive cancers. However, the full-length molecular dynamic structure of ERα remains elusive. In this study, we employ high-speed atomic force microscopy (HS-AFM) to visualize interactions with estrogen response element (ERE) under both ligand-present and ligand-absent conditions. binds ERE even absence estrogen, although presence ligand significantly enhances binding precision stability. Our real-time, high-resolution HS-AFM imaging captures structural transitions from monomeric dimeric forms, elucidating mechanisms by which modulates DNA-binding specificity. Based on these findings, propose a ligand-induced dimerization (LID) model, wherein facilitates optimal loading onto DNA. These insights deepen our understanding hormone signaling cancer hold promise for development future therapeutic strategies targeting hormone-related malignancies.

Language: Английский

Zooming into Gene Activation: Estrogen Receptor α Dimerization and DNA Binding Visualized by High-Speed Atomic Force Microscopy DOI Creative Commons
Goro Nishide,

Tomoka Ishibashi,

Keesiang Lim

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Estrogen receptor α (ERα) is pivotal in gene regulation, particularly estrogen-responsive cancers. However, the full-length molecular dynamic structure of ERα remains elusive. In this study, we employ high-speed atomic force microscopy (HS-AFM) to visualize interactions with estrogen response element (ERE) under both ligand-present and ligand-absent conditions. binds ERE even absence estrogen, although presence ligand significantly enhances binding precision stability. Our real-time, high-resolution HS-AFM imaging captures structural transitions from monomeric dimeric forms, elucidating mechanisms by which modulates DNA-binding specificity. Based on these findings, propose a ligand-induced dimerization (LID) model, wherein facilitates optimal loading onto DNA. These insights deepen our understanding hormone signaling cancer hold promise for development future therapeutic strategies targeting hormone-related malignancies.

Language: Английский

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