ATP binding facilitates target search of SWR1 chromatin remodeler by promoting one-dimensional diffusion on DNA.

Claudia C Carcamo, Matthew F Poyton, Anand Ranjan, Giho Park, Robert K Louder, Xinyu A Feng, Jee Min Kim, Thuc Dzu, Carl Wu, Taekjip Ha

eLife 2022 Jul 25

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One-dimensional (1D) target search is a well-characterized phenomenon for many DNA-binding proteins but is poorly understood for chromatin remodelers. Herein, we characterize the 1D scanning properties of SWR1, a conserved yeast chromatin remodeler that performs histone exchange on +1 nucleosomes adjacent to a nucleosome-depleted region (NDR) at gene promoters. We demonstrate that SWR1 has a kinetic binding preference for DNA of NDR length as opposed to gene-body linker length DNA. Using single and dual color single-particle tracking on DNA stretched with optical tweezers, we directly observe SWR1 diffusion on DNA. We found that various factors impact SWR1 scanning, including ATP which promotes diffusion through nucleotide binding rather than ATP hydrolysis. A DNA-binding subunit, Swc2, plays an important role in the overall diffusive behavior of the complex, as the subunit in isolation retains similar, although faster, scanning properties as the whole remodeler. ATP-bound SWR1 slides until it encounters a protein roadblock, of which we tested dCas9 and nucleosomes. The median diffusion coefficient, 0.024 μm2/s, in the regime of helical sliding, would mediate rapid encounter of NDR-flanking nucleosomes at length scales found in cellular chromatin. © 2022, Carcamo et al.

Citation

Claudia C Carcamo, Matthew F Poyton, Anand Ranjan, Giho Park, Robert K Louder, Xinyu A Feng, Jee Min Kim, Thuc Dzu, Carl Wu, Taekjip Ha. ATP binding facilitates target search of SWR1 chromatin remodeler by promoting one-dimensional diffusion on DNA. eLife. 2022 Jul 25;11