Basis of specificity for a conserved and promiscuous chromatin remodeling protein
- University of Oregon, United States
Abstract
Eukaryotic genomes are organized dynamically through the repositioning of nucleosomes. Isw2 is an enzyme that has been previously defined as a genome-wide, non-specific nucleosome spacing factor. Here, we show that Isw2 instead acts as an obligately targeted nucleosome remodeler in vivo through physical interactions with sequence-specific factors. We demonstrate that Isw2- recruiting factors use small and previously uncharacterized epitopes, which direct Isw2 activity through highly conserved acidic residues in the Isw2 accessory protein Itc1. This interaction orients Isw2 on target nucleosomes, allowing for precise nucleosome positioning at targeted loci. Finally, we show that these critical acidic residues have been lost in the Drosophila lineage, potentially explaining the inconsistently characterized function of Isw2-like proteins. Altogether, these data suggest an 'interacting barrier model' where Isw2 interacts with a sequence-specific factor to accurately and reproducibly position a single, targeted nucleosome to define the precise border of phased chromatin arrays.
Data availability
Sequencing data have been deposited in GEO under accession code GSE149804
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Basis of Specificity for a Conserved Promiscuous Chromatin Remodeling ProteinNCBI Gene Expression Omnibus, GSE149804.
Article and author information
Author details
Johnathan G Crandall
Funding
National Institutes of Health (T32 GM007759)
- Drake A Donovan
- Orion GB Banks
National Institutes of Health (T32 GM007413)
- Drake A Donovan
- Vi N Truong
National Institute of General Medical Sciences (R01 GM129242)
- Jeffrey N McKnight
Donald and Delia Baxter Foundation
- Jeffrey N McKnight
Medical Research Foundation of Oregon
- Jeffrey N McKnight
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jerry L Workman, Stowers Institute for Medical Research, United States
Publication history
- Received: October 15, 2020
- Accepted: February 11, 2021
- Accepted Manuscript published: February 12, 2021 (version 1)
- Version of Record published: March 17, 2021 (version 2)
Copyright
© 2021, Donovan 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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Basis of specificity for a conserved and promiscuous chromatin remodeling protein
eLife 10:e64061.
https://doi.org/10.7554/eLife.64061
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