{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:18:46Z","timestamp":1785417526060,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,19]]},"group-title":"Molecular Biology","reference-count":70,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R35GM119580"],"award-info":[{"award-number":["R35GM119580"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The INO80 chromatin-remodeling complex is a multi-subunit regulator of DNA-templated processes, yet the mechanisms that control remodeler function\n                  <jats:italic>in vivo<\/jats:italic>\n                  are not completely known. In this study, we report that the Ies6 subunit of the INO80 complex encodes a prion-like domain (PLD) within a larger region of predicted disorder. After transient inducible overexpression, both full-length Ies6 and the PLD domain alone aggregate in a manner that evades proteasome-mediated degradation, suggestive of prion-like behavior. Cytosolic aggregates are also visible with fluorescent microscopy following expression of the PLD alone. Loss of the protein chaperone Hsp70 increases Ies6 aggregation. In addition, deletion of\n                  <jats:italic>ARP5<\/jats:italic>\n                  , another INO80 subunit and binding partner of Ies6, also results in elevated protein aggregation. Finally, transcriptome analysis indicates that loss of PLD-mediated aggregation alters the expression of telomere-proximal and metabolic stress-responsive genes, including those involved in glucose starvation and respiratory programs, even under glucose-replete conditions. Together, these findings support a model in which Ies6 couples the INO80 complex to metabolic gene regulation via prion-like behavior, providing a potential new mechanism for tuning chromatin-based metabolic adaptation.\n                <\/jats:p>","DOI":"10.64898\/2026.05.18.722789","type":"posted-content","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:55:16Z","timestamp":1779191716000},"source":"Crossref","is-referenced-by-count":0,"title":["The Prion-Like Properties of the INO80 Chromatin Remodeler Regulate Metabolic Gene Expression"],"prefix":"10.64898","author":[{"given":"Dylan C.","family":"Englund","sequence":"first","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6078-5159","authenticated-orcid":false,"given":"Keith C.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3497-5888","authenticated-orcid":false,"given":"Daniel F.","family":"Jarosz","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1228-5093","authenticated-orcid":false,"given":"Ashby J.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070810352294000_2026.05.18.722789v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.02.044"},{"key":"2026070810352294000_2026.05.18.722789v2.2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.69549"},{"key":"2026070810352294000_2026.05.18.722789v2.3","doi-asserted-by":"crossref","first-page":"e1007216","DOI":"10.1371\/journal.pgen.1007216","article-title":"The INO80 chromatin remodeler sustains metabolic stability by promoting TOR signaling and regulating histone acetylation","volume":"14","year":"2018","journal-title":"PLoS Genet"},{"key":"2026070810352294000_2026.05.18.722789v2.4","doi-asserted-by":"crossref","first-page":"103030","DOI":"10.1016\/j.sbi.2025.103030","article-title":"Mechanistic insights into INO80-type chromatin remodelers","volume":"92","year":"2025","journal-title":"Current Opinion in Structural Biology"},{"key":"2026070810352294000_2026.05.18.722789v2.5","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1839109"},{"key":"2026070810352294000_2026.05.18.722789v2.6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.222505"},{"key":"2026070810352294000_2026.05.18.722789v2.7","doi-asserted-by":"publisher","DOI":"10.1126\/science.7754373"},{"key":"2026070810352294000_2026.05.18.722789v2.8","doi-asserted-by":"publisher","DOI":"10.1038\/ng.112"},{"key":"2026070810352294000_2026.05.18.722789v2.9","doi-asserted-by":"crossref","first-page":"21838","DOI":"10.1038\/s41598-020-77993-0","article-title":"Elucidating the regulatory mechanism of Swi1 prion in global transcription and stress responses","volume":"10","year":"2020","journal-title":"Sci Rep"},{"key":"2026070810352294000_2026.05.18.722789v2.10","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae385"},{"key":"2026070810352294000_2026.05.18.722789v2.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0439-x"},{"key":"2026070810352294000_2026.05.18.722789v2.12","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.17978"},{"key":"2026070810352294000_2026.05.18.722789v2.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.12.079"},{"key":"2026070810352294000_2026.05.18.722789v2.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.014"},{"key":"2026070810352294000_2026.05.18.722789v2.15","doi-asserted-by":"publisher","DOI":"10.1016\/J.MOLCEL.2022.04.026"},{"key":"2026070810352294000_2026.05.18.722789v2.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2010.07.009"},{"key":"2026070810352294000_2026.05.18.722789v2.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.07.024"},{"key":"2026070810352294000_2026.05.18.722789v2.18","unstructured":"Kaiser Chris , Michaelis Susan , Mitchell Aaron , Cold Spring Harbor Laboratory. 1994. 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