Structural Biology

Using cryo-EM, the Hopfner lab shows that the INO80 motor module senses DNA unwrapping from nucleosomes and adapts its binding to position the motor at the correct DNA entry site—enabling efficient chromatin remodeling during transcription.

Nucleosomes package DNA in eukaryotic cells and play a central role in regulating gene activity. To reorganize this structure, cells rely on ATP-dependent chromatin remodelers—powerful molecular machines that reposition nucleosomes when genes need to be turned on or off.

One such remodeler, the human INO80 complex, is well known for sliding canonical nucleosomes along DNA. But what happens when nucleosomes are altered? During active transcription, particles such as hexasomes—nucleosomes missing one H2A–H2B dimer—can form. Until now, it remained unclear whether INO80 could effectively act on these noncanonical substrates.

Using cryo–electron microscopy, this study reveals that INO80’s motor module is remarkably adaptable. It senses the degree of DNA unwrapping from the nucleosome and adjusts its binding topology accordingly. This flexibility positions the motor at the correct DNA entry site, enabling efficient remodeling across a spectrum of nucleosomal states.

Original publication:

Recognition and remodelling of nucleosomes and hexasomes by the human INO80 complex
Aggarwal P, Sharma M, Woike S, Kunert F, Brem A, Moldt M, Hopfner KP. 
Nucleic Acids Res. 2026 Feb 24;54(5):gkag138. doi: https://doi.org/10.1093/nar/gkag138