Single-molecule imaging of chromatin remodelers reveals role of ATPase in promoting fast kinetics of target search and dissociation from chromatin

eLife

Jee Min Kim¹  Sheng Liu¹  Xiaona Tang¹  Kai Yu Li¹  Pat Visanpattanasin¹  Vivian Jou¹  Jonathan Snedeker¹  Carl Wu²  Timothee Lionnet³  Qinsi Zheng⁴  Luke D Lavis⁴ 

[1] Department of Biology, Johns Hopkins University, Baltimore, United States;Department of Biology, Johns Hopkins University, Baltimore, United States;Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, United States;Institute of Systems Genetics, Langone Medical Center, New York University, New York, United States;Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States;

关键词: ATP-dependent chromatin remodelers;    single-molecule tracking;    live-cell imaging;    search;    residence times;    promoter region occupancy;    S. cerevisiae;   

DOI  :  10.7554/eLife.69387

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Conserved ATP-dependent chromatin remodelers establish and maintain genome-wide chromatin architectures of regulatory DNA during cellular lifespan, but the temporal interactions between remodelers and chromatin targets have been obscure. We performed live-cell single-molecule tracking for RSC, SWI/SNF, CHD1, ISW1, ISW2, and INO80 remodeling complexes in budding yeast and detected hyperkinetic behaviors for chromatin-bound molecules that frequently transition to the free state for all complexes. Chromatin-bound remodelers display notably higher diffusion than nucleosomal histones, and strikingly fast dissociation kinetics with 4–7 s mean residence times. These enhanced dynamics require ATP binding or hydrolysis by the catalytic ATPase, uncovering an additional function to its established role in nucleosome remodeling. Kinetic simulations show that multiple remodelers can repeatedly occupy the same promoter region on a timescale of minutes, implicating an unending ‘tug-of-war’ that controls a temporally shifting window of accessibility for the transcription initiation machinery.

【 授权许可】

CC BY