title: Nucleosome recognition by the Piccolo NuA4 histone acetyltransferase complex.
abstract: The mechanisms by which multisubunit histone acetyltransferase (HAT) complexes recognize and perform efficient acetylation on nucleosome substrates are largely unknown. Here, we use a variety of biochemical approaches and compare histone-based substrates of increasing complexity to determine the critical components of nucleosome recognition by the MOZ, Ybf2/Sas3, Sas2, Tip60 family HAT complex, Piccolo NuA4 (picNuA4). We find the histone tails to be dispensable for binding to both nucleosomes and free histones and that the H2A, H3, and H2B tails do not influence the ability of picNuA4 to tetra-acetylate the H4 tail within the nucleosome. Most notably, we discovered that the histone-fold domain (HFD) regions of histones, particularly residues 21-52 of H4, are critical for tight binding and efficient tail acetylation. Presented evidence suggests that picNuA4 recognizes the open surface of the nucleosome on which the HFD of H4 is located. This binding mechanism serves to direct substrate access to the tails of H4 and H2A and allows the enzyme to be "tethered", thereby increasing the effective concentration of the histone tail and permitting successive cycles of H4 tail acetylation.
authors.affiliation: Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin 53706, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Berndsen
authors.forename: William
authors.initials: W
authors.lastname: Selleck
authors.forename: Steven J
authors.initials: SJ
authors.lastname: McBryant
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Hansen
authors.forename: Song
authors.initials: S
authors.lastname: Tan
authors.forename: John M
authors.initials: JM
authors.lastname: Denu
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases; D000818:Animals; D036382:Ephrin-A1 / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000302:isolation & purification / Q000378:metabolism; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism*; D021122:Protein Subunits; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013379:Substrate Specificity; D029867:Xenopus Proteins / Q000302:isolation & purification / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D036382:Ephrin-A1; D006657:Histones; D046912:Multiprotein Complexes; D009707:Nucleosomes; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D029867:Xenopus Proteins; D000123:Acetyltransferases; C469780:Yng2 protein, S cerevisiae; C496551:Esa1 protein, S cerevisiae; D051548:Histone Acetyltransferases; C504740:NuA4 protein, S cerevisiae