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Subnucleosome preference of human chromatin remodeller SMARCAD1

Pengjing Hu, Jingxi Sun, Hongyao Sun, Kangjing Chen, Youyang Sia, Xian Xia, Qiaoran Xi () and Zhucheng Chen ()
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Pengjing Hu: Tsinghua University
Jingxi Sun: Tsinghua University
Hongyao Sun: Tsinghua University
Kangjing Chen: Tsinghua University
Youyang Sia: Tsinghua University
Xian Xia: University of California
Qiaoran Xi: Tsinghua University
Zhucheng Chen: Tsinghua University

Nature, 2025, vol. 644, issue 8077, 818-826

Abstract: Abstract Chromatin remodellers are pivotal in the regulation of nucleosome dynamics in cells, and they are important for chromatin packaging, transcription, replication and DNA repair1. Here we show that the human chromatin remodeller SMARCAD1 exhibits a substrate preference for subnucleosomal particles over the canonical nucleosome. Cryo-electron microscopy structures of SMARCAD1 bound to the nucleosome and hexasome provide mechanistic insights into the substrate selectivity. SMARCAD1 binds to the hexasome through multiple family-specific elements that are essential for the functions in vitro and in cells. The enzyme binds to the canonical nucleosome in an inactive conformation, which accounts for its diminished activity towards the nucleosome. Notably, the histone chaperone FACT complex acts synergistically with H2A–H2B to promote the activity of SMARCAD1 in nucleosome remodelling. Together, our findings reveal an avenue for chromatin regulation, whereby subnucleosomes are remodelled through an ATP-dependent process.

Date: 2025
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DOI: 10.1038/s41586-025-09100-0

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