title: The Eaf3/5/7 Subcomplex Stimulates NuA4 Interaction with Methylated Histone H3 Lys-36 and RNA Polymerase II.
abstract: NuA4 is the only essential lysine acetyltransferase complex in Saccharomyces cerevisiae, where it has been shown to stimulate transcription initiation and elongation. Interaction with nucleosomes is stimulated by histone H3 Lys-4 and Lys-36 methylation, but the mechanism of this interaction is unknown. Eaf3, Eaf5, and Eaf7 form a subcomplex within NuA4 that may also function independently of the lysine acetyltransferase complex. The Eaf3/5/7 complex and the Rpd3C(S) histone deacetylase complex have both been shown to bind di- and trimethylated histone H3 Lys-36 stimulated by Eaf3. We investigated the role of the Eaf3/5/7 subcomplex in NuA4 binding to nucleosomes. Different phenotypes of eaf3/5/7Δ mutants support functions for the complex as both part of and independent of NuA4. Further evidence for Eaf3/5/7 within NuA4 came from mutations in the subcomplex leading to ∼40% reductions in H4 acetylation in bulk histones, probably caused by binding defects to both nucleosomes and RNA polymerase II. In vitro binding assays showed that Eaf3/5/7 specifically stimulates NuA4 binding to di- and trimethylated histone H3 Lys-36 and that this binding is important for NuA4 occupancy in transcribed ORFs. Consistent with the role of NuA4 in stimulating transcription elongation, loss of EAF5 or EAF7 resulted in a processivity defect. Overall, these results reveal the function of Eaf3/5/7 within NuA4 to be important for both NuA4 and RNA polymerase II binding.
authors.affiliation: From the Biomedical Sciences and.
authors.forename: Anish
authors.initials: A
authors.lastname: Sathianathan
authors.affiliation: From the Biomedical Sciences and.
authors.forename: Priyadarshini
authors.initials: P
authors.lastname: Ravichandran
authors.affiliation: From the Biomedical Sciences and.
authors.forename: Jake M
authors.initials: JM
authors.lastname: Lippi
authors.affiliation: From the Biomedical Sciences and.
authors.forename: Leah
authors.initials: L
authors.lastname: Cohen
authors.affiliation: From the Biomedical Sciences and.
authors.forename: Angelo
authors.initials: A
authors.lastname: Messina
authors.affiliation: From the Biomedical Sciences and.
authors.forename: Sherwin
authors.initials: S
authors.lastname: Shaju
authors.affiliation: Health Sciences Departments, LIU Post, Brookville, New York 11548.
authors.forename: Marci J
authors.initials: MJ
authors.lastname: Swede
authors.affiliation: From the Biomedical Sciences and daniel.ginsburg@liu.edu.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Ginsburg
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; D009097:Multienzyme Complexes; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; C428131:Eaf3 protein, S cerevisiae; C528251:Eaf5 protein, S cerevisiae; C528253:Eaf7 protein, S cerevisiae; D051548:Histone Acetyltransferases; C504740:NuA4 protein, S cerevisiae; D012319:RNA Polymerase II
keywords: Eaf3; NuA4; Pol II CTD; Set2; TINTIN; acetyltransferase; chromatin modification; histone acetylation; histone methylation; transcription regulation