Mechanistic insights into chromatin modulation by the "orphan" remodeler ATRX.

Cryo-EM structure shows ATRX recognizes and unwraps approximately 18 base pairs of nucleosomal DNA near entry/exit sites in the presence of ADP•BeF3.

• Why it matters: Understanding ATRX’s mechanism of chromatin modulation is crucial because its dysfunction is linked to alpha-thalassemia/mental retardation syndrome X-linked, and its role in protecting cells from G-quadruplex DNA stress is vital for genome stability.
• What they did: The study used cryo-electron microscopy to reveal how human ATRX interacts with nucleosomes, including a "pin-like" structure that deforms DNA and regions that contact histones, with key features essential for chromatin remodeling.
• The result: Findings highlight that ATRX’s DNA-intercalating and histone-contacting regions are critical for preventing G-quadruplex DNA stress, advancing understanding of its chromatin remodeling mechanism.