Zooming into Gene Activation: Estrogen Receptor α Dimerization and DNA Binding Visualized by High-Speed Atomic Force Microscopy

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

Unraveling dynamics of nuclear pore and chromatin via HS-AFM

Anatomical Science International, Journal Year: 2025, Volume and Issue: unknown

Published: May 19, 2025

Abstract High-speed atomic force microscopy (HS-AFM) enables real-time visualization of biological processes with nanometer-level resolution. This review highlights how HS-AFM has been instrumental in uncovering the dynamic interplay between nuclear pore complexes (NPCs)—which regulate nucleocytoplasmic transport—and genome guardians, including DNA repair proteins and chromatin regulators. Structurally, NPCs resemble a multi-layered spider cobweb, serving as crucial molecular gatekeepers for maintaining cellular homeostasis, while guardians safeguard genomic integrity through organization. Through HS-AFM, researchers have gained unprecedented insights into NPC dynamics, revealing their adaptability during transport, reorganization, viral infection. It also elucidated interact NPCs, influencing organization at periphery regulating trafficking. These discoveries underscore critical role NPC-genome interactions stability, gene expression, broad implications diseases such cancer, infections, neurodegenerative disorders. In conclusion, transformed our ability to study landscape nanoscale, bridging gap structural biology functional genomics. By capturing dynamics chromatin, provides an essential tool unraveling mechanisms that govern transport regulation. Future advancements technology, higher temporal resolution, correlative imaging, AI-driven analysis, will further expand its potential biomedical research, paving way novel diagnostic therapeutic strategies.

Language: Английский