National Institutes of Health/National Cancer Institute (NIH/NCI)
ES036404
United States
Citation
Journal: Mol Cell / Year: 2025 Title: Structural basis of human CHD1 nucleosome recruitment and pausing. Authors: Allison M James / Lucas Farnung / Abstract: Chromatin remodelers regulate gene expression and genome maintenance by controlling nucleosome positioning, but the structural basis for their regulated and directional activity remains poorly ...Chromatin remodelers regulate gene expression and genome maintenance by controlling nucleosome positioning, but the structural basis for their regulated and directional activity remains poorly understood. Here, we present three cryoelectron microscopy (cryo-EM) structures of human chromodomain helicase DNA-binding protein 1 (CHD1) bound to nucleosomes that reveal previously unobserved recruitment and regulatory states. We identify a structural element, termed the "anchor element," that connects the CHD1 ATPase motor to the nucleosome entry-side acidic patch. The anchor element coordinates with other regulatory modules, including the gating element, which undergoes a conformational switch critical for remodeling. Our structures demonstrate how the DNA-binding region of CHD1 binds entry- and exit-side DNA during remodeling to achieve directional sliding. The observed structural elements are conserved across chromatin remodelers, suggesting a unified mechanism for nucleosome recognition and remodeling. Our findings show how chromatin remodelers couple nucleosome recruitment to regulated DNA translocation, providing a framework for understanding chromatin remodeler mechanisms beyond DNA translocation.
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