title: An rtt109-independent role for vps75 in transcription-associated nucleosome dynamics.
abstract: The histone chaperone Vps75 forms a complex with, and stimulates the activity of, the histone acetyltransferase Rtt109. However, Vps75 can also be isolated on its own and might therefore possess Rtt109-independent functions. Analysis of epistatic miniarray profiles showed that VPS75 genetically interacts with factors involved in transcription regulation whereas RTT109 clusters with genes linked to DNA replication/repair. Additional genetic and biochemical experiments revealed a close relationship between Vps75 and RNA polymerase II. Furthermore, Vps75 is recruited to activated genes in an Rtt109-independent manner, and its genome-wide association with genes correlates with transcription rate. Expression microarray analysis identified a number of genes whose normal expression depends on VPS75. Interestingly, histone H2B dynamics at some of these genes are consistent with a role for Vps75 in histone H2A/H2B eviction/deposition during transcription. Indeed, reconstitution of nucleosome disassembly using the ATP-dependent chromatin remodeler Rsc and Vps75 revealed that these proteins can cooperate to remove H2A/H2B dimers from nucleosomes. These results indicate a role for Vps75 in nucleosome dynamics during transcription, and importantly, this function appears to be largely independent of Rtt109.
authors.affiliation: Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms, Hertfordshire, U.K.
authors.forename: Luke A
authors.initials: LA
authors.lastname: Selth
authors.forename: Yahli
authors.initials: Y
authors.lastname: Lorch
authors.forename: Maria T
authors.initials: MT
authors.lastname: Ocampo-Hafalla
authors.forename: Richard
authors.initials: R
authors.lastname: Mitter
authors.forename: Michael
authors.initials: M
authors.lastname: Shales
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
authors.forename: Roger D
authors.initials: RD
authors.lastname: Kornberg
authors.forename: Jesper Q
authors.initials: JQ
authors.lastname: Svejstrup
mesh_terms: D000107:Acetylation; D001665:Binding Sites / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D016681:Genome, Fungal / Q000235:genetics; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009707:Nucleosomes / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D018832:Molecular Chaperones; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; C525548:Vps75 protein, S cerevisiae; D051548:Histone Acetyltransferases; C517120:Rtt109 protein, S cerevisiae; D012319:RNA Polymerase II; C511736:RPB1 protein, S cerevisiae; D008239:Lysine