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dc.contributor.authorBaier, Alexander S
dc.contributor.authorGioacchini, Nathan
dc.contributor.authorEek, Priit
dc.contributor.authorLeith, Erik M
dc.contributor.authorTan, Song
dc.contributor.authorPeterson, Craig L
dc.date.accessioned2024-06-27T20:14:45Z
dc.date.available2024-06-27T20:14:45Z
dc.date.issued2024-05-29
dc.identifier.citationBaier AS, Gioacchini N, Eek P, Leith EM, Tan S, Peterson CL. Dual engagement of the nucleosomal acidic patches is essential for deposition of histone H2A.Z by SWR1C. Elife. 2024 May 29;13:RP94869. doi: 10.7554/eLife.94869. PMID: 38809771; PMCID: PMC11139478.en_US
dc.identifier.eissn2050-084X
dc.identifier.doi10.7554/eLife.94869en_US
dc.identifier.pmid38809771
dc.identifier.urihttp://hdl.handle.net/20.500.14038/53524
dc.description.abstractThe yeast SWR1C chromatin remodeling enzyme catalyzes the ATP-dependent exchange of nucleosomal histone H2A for the histone variant H2A.Z, a key variant involved in a multitude of nuclear functions. How the 14-subunit SWR1C engages the nucleosomal substrate remains largely unknown. Studies on the ISWI, CHD1, and SWI/SNF families of chromatin remodeling enzymes have demonstrated key roles for the nucleosomal acidic patch for remodeling activity, however a role for this nucleosomal epitope in nucleosome editing by SWR1C has not been tested. Here, we employ a variety of biochemical assays to demonstrate an essential role for the acidic patch in the H2A.Z exchange reaction. Utilizing asymmetrically assembled nucleosomes, we demonstrate that the acidic patches on each face of the nucleosome are required for SWR1C-mediated dimer exchange, suggesting SWR1C engages the nucleosome in a 'pincer-like' conformation, engaging both patches simultaneously. Loss of a single acidic patch results in loss of high affinity nucleosome binding and nucleosomal stimulation of ATPase activity. We identify a conserved arginine-rich motif within the Swc5 subunit that binds the acidic patch and is key for dimer exchange activity. In addition, our cryoEM structure of a Swc5-nucleosome complex suggests that promoter proximal, histone H2B ubiquitylation may regulate H2A.Z deposition. Together these findings provide new insights into how SWR1C engages its nucleosomal substrate to promote efficient H2A.Z deposition.en_US
dc.language.isoen
dc.relation.ispartofeLifeen_US
dc.relation.urlhttps://doi.org/10.7554/elife.94869en_US
dc.rightsCopyright Baier et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.en_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectH2A.Zen_US
dc.subjectS. cerevisiaeen_US
dc.subjectSWR1Cen_US
dc.subjectbiochemistryen_US
dc.subjectchemical biologyen_US
dc.subjectchromatinen_US
dc.subjectnucleosomeen_US
dc.subjecttranscriptionen_US
dc.subjectyeasten_US
dc.titleDual engagement of the nucleosomal acidic patches is essential for deposition of histone H2A.Z by SWR1Cen_US
dc.typeJournal Articleen_US
dc.source.journaltitleeLife
dc.source.volume13
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryEngland
dc.identifier.journaleLife
refterms.dateFOA2024-06-27T20:14:46Z
dc.contributor.departmentMorningside Graduate School of Biomedical Sciencesen_US
dc.contributor.departmentProgram in Molecular Medicineen_US
dc.contributor.departmentT.H. Chan School of Medicineen_US
dc.contributor.studentAlexander S Baier
dc.contributor.studentNathan Gioacchini
dc.description.thesisprogramMD/PhD
dc.description.thesisprogramInterdisciplinary Graduate Program


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Copyright Baier et al. This
article is distributed under the
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original author and source are
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Except where otherwise noted, this item's license is described as Copyright Baier et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.