Regulation of DNA translocation of chromatin remodeler enzyme Chd1 by exit DNA unwrapping

Abstract

Nucleosomes are the fundamental unit of chromatin. Chromatin remodeler plays a crucial role in the regulation of gene expression in eukaryotes. It is involved in important physiological processes, such as development, immune response, and metabolic regulation. During gene expression regulation, chromatin remodelers slide nucleosomes along genomic DNA and play a major role in chromatin organization. Chd1 senses the extranucleosomal linker DNA and controls nucleosome spacing in cells. However, the mechanism of linker DNA sensing by Chd1 is not completely understood. Here, we report the cryo-electron microscope (cryoEM) structures of Chd1 engaging nucleosomes in different states. Chd1 induces two exit-DNA conformations, either fully wrapped or partially unwrapped states. Notably, in the unwrapped conformation, the exit DNA interacts with a positively charged loop of the motor, named the exit-DNA binding loop, and traps Chd1 in the closed state in the ATPase cycle, suggesting attenuation of its remodeling activity. Explored single-molecule fluorescence resonance energy transfer (smFRET) and biochemical data supported the regulation of Chd1 remodeling activity by the exit-DNA conformations, which is important for the linker DNA sensitivity. Mutants of the Chd1 exit-DNA binding loop compromised nucleosome organization in yeast cells. Together, our findings provide valuable insights into Chd1 regulation by exit DNA unwrapping. These results provide a new perspective for the study of cell development and metabolism.

Keywords

chromatin remodeling / Chd1 / nucleosome spacing / chromatin organization / gene expression regulation

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RIGHTS & PERMISSIONS

Published by Oxford University Press on behalf of Higher Education Press 2025. This work is written by (a) US Government employee(s) and is in the public domain in the US.