title: The INO80 Complex Requires the Arp5-Ies6 Subcomplex for Chromatin Remodeling and Metabolic Regulation.
abstract: ATP-dependent chromatin remodeling complexes are essential for transcription regulation, and yet it is unclear how these multisubunit complexes coordinate their activities to facilitate diverse transcriptional responses. In this study, we found that the conserved Arp5 and Ies6 subunits of the Saccharomyces cerevisiae INO80 chromatin-remodeler form an abundant and distinct subcomplex in vivo and stimulate INO80-mediated activity in vitro. Moreover, our genomic studies reveal that the relative occupancy of Arp5-Ies6 correlates with nucleosome positioning at transcriptional start sites and expression levels of >1,000 INO80-regulated genes. Notably, these genes are significantly enriched in energy metabolism pathways. Specifically, arp5Δ, ies6Δ, and ino80Δ mutants demonstrate decreased expression of genes involved in glycolysis and increased expression of genes in the oxidative phosphorylation pathway. Deregulation of these metabolic pathways results in constitutively elevated mitochondrial potential and oxygen consumption. Our results illustrate the dynamic nature of the INO80 complex assembly and demonstrate for the first time that a chromatin remodeler regulates glycolytic and respiratory capacity, thereby maintaining metabolic stability.
authors.affiliation: Department of Biology, Stanford University, Stanford, California, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Biology, Stanford University, Stanford, California, USA.
authors.forename: Devin A
authors.initials: DA
authors.lastname: King
authors.affiliation: Department of Biology, Stanford University, Stanford, California, USA.
authors.forename: Sean L
authors.initials: SL
authors.lastname: Beckwith
authors.affiliation: Department of Biology, Stanford University, Stanford, California, USA.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Gowans
authors.affiliation: Department of Cell Biology, Southern Medical University, Guangzhou, China Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Kuangyu
authors.initials: K
authors.lastname: Yen
authors.affiliation: Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California, USA.
authors.forename: Coral
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Biology, Stanford University, Stanford, California, USA ashbym@stanford.edu.
authors.forename: Ashby J
authors.identifier: http://orcid.org/0000-0003-1228-5093
authors.initials: AJ
authors.lastname: Morrison
mesh_terms: D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D053858:Metabolic Networks and Pathways; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000609267:Arp5 protein, S cerevisiae; D002868:Chromosomal Proteins, Non-Histone; C483404:INO80 complex, S cerevisiae; C000609268:Ies6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins