The nucleosomal acidic patch relieves auto-inhibition by the ISWI remodeler SNF2h
- University of California, San Francisco, United States
Abstract
ISWI family chromatin remodeling motors use sophisticated autoinhibition mechanisms to control nucleosome sliding. Yet how the different autoinhibitory domains are regulated is not well understood. Here we show that an acidic patch formed by histones H2A and H2B of the nucleosome relieves the autoinhibition imposed by the AutoN and the NegC regions of the human ISWI remodeler SNF2h. Further, by single molecule FRET we show that the acidic patch helps control the distance travelled per translocation event. We propose a model in which the acidic patch activates SNF2h by providing a landing pad for the NegC and AutoN auto-inhibitory domains. Interestingly, the acidic patch also inhibits the INO80 complex, indicating that this substrate feature can regulate remodeling enzymes with substantially different mechanisms. We therefore hypothesize that regulating access to the acidic patch of the nucleosome plays a key role in coordinating the activities of different remodelers in the cell.
Data availability
Relevant source data is provided in the main and supplemental figures. Crosslinked residue pair identification along with number of spectral counts per identification are reported in Supplemental File 1, as well as in a web resource with links to annotated product ion spectra (see Experimental Methods). Raw mass spectrometry files are available on the Massive server (UCSD). Code used for the analysis of smFRET data can be found at the following link, which is also found in the main text. https://github.com/stephlj/Traces
Article and author information
Author details
Funding
Leukemia and Lymphoma Society (Carrer Development Program Fellow Award)
- Stephanie L Johnson
National Science Foundation (Predoctoral Fellowship)
- Nathan Gamarra
National Institute of General Medical Sciences (R01GM073767)
- Geeta J Narlikar
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Alma L Burlingame
University of California, San Francisco (Program for Breakthrough Biomedical Research (PBBR))
- Alma L Burlingame
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Gamarra et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The nucleosomal acidic patch relieves auto-inhibition by the ISWI remodeler SNF2h
eLife 7:e35322.
https://doi.org/10.7554/eLife.35322
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