title: Histone H3K4 and H3K36 Methylation Independently Recruit the NuA3 Histone Acetyltransferase inSaccharomyces cerevisiae.
abstract: Histone post-translational modifications (PTMs) alter chromatin structure by promoting the interaction of chromatin-modifying complexes with nucleosomes. The majority of chromatin-modifying complexes contain multiple domains that preferentially interact with modified histones, leading to speculation that these domains function in concert to target nucleosomes with distinct combinations of histone PTMs. InSaccharomyces cerevisiae, the NuA3 histone acetyltransferase complex contains three domains, the PHD finger in Yng1, the PWWP domain in Pdp3, and the YEATS domain in Taf14; whichin vitrobind to H3K4 methylation, H3K36 methylation, and acetylated and crotonylated H3K9, respectively. While thein vitrobinding has been well characterized, the relativein vivocontributions of these histone PTMs in targeting NuA3 is unknown. Here, through genome-wide colocalization and by mutational interrogation, we demonstrate that the PHD finger of Yng1, and the PWWP domain of Pdp3 independently target NuA3 to H3K4 and H3K36 methylated chromatin, respectively. In contrast, we find no evidence to support the YEATS domain of Taf14 functioning in NuA3 recruitment. Collectively our results suggest that the presence of multiple histone PTM binding domains within NuA3, rather than restricting it to nucleosomes containing distinct combinations of histone PTMs, can serve to increase the range of nucleosomes bound by the complex. Interestingly, however, the simple presence of NuA3 is insufficient to ensure acetylation of the associated nucleosomes, suggesting a secondary level of acetylation regulation that does not involve control of HAT-nucleosome interactions.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver V6T 1Z3, Canada.|Hunter Medical Research Institute, University of Newcastle, 2308, Australia.
authors.forename: Benjamin J E
authors.initials: BJ
authors.lastname: Martin
authors.affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver V6T 1Z3, Canada.|Hunter Medical Research Institute, University of Newcastle, 2308, Australia.
authors.forename: Kristina L
authors.initials: KL
authors.lastname: McBurney
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, 2308, Australia.|Department of Medical Genetics, University of British Columbia, Vancouver V6T 1Z3, Canada.
authors.forename: Vicki E
authors.initials: VE
authors.lastname: Maltby
authors.affiliation: Hunter Medical Research Institute, University of Newcastle, 2308, Australia.|Department of Medical Genetics, University of British Columbia, Vancouver V6T 1Z3, Canada.
authors.forename: Kristoffer N
authors.initials: KN
authors.lastname: Jensen
authors.affiliation: Hunter Medical Research Institute, University of Newcastle, 2308, Australia.|Department of Medical Genetics, University of British Columbia, Vancouver V6T 1Z3, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Brind'Amour
authors.affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver V6T 1Z3, Canada ljhowe@mail.ubc.ca.
authors.forename: LeAnn J
authors.initials: LJ
authors.lastname: Howe
mesh_terms: D000107:Acetylation; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; D009707:Nucleosomes; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D051548:Histone Acetyltransferases
keywords: NuA3; Saccharomyces cerevisiae; histone acetylation; histone acetyltransferase; histone methylation