title: Recognition Elements in the Histone H3 and H4 Tails for Seven Different Importins.
abstract: N-terminal tails of histones H3 and H4 are known to bind several different Importins to import the histones into the cell nucleus. However, it is not known what binding elements in the histone tails are recognized by the individual Importins. Biochemical studies of H3 and H4 tails binding to seven Importins, Impβ, Kapβ2, Imp4, Imp5, Imp7, Imp9, and Impα, show the H3 tail binding more tightly than the H4 tail. The H3 tail binds Kapβ2 and Imp5 with KDvalues of 77 and 57 nm, respectively, and binds the other five Importins more weakly. Mutagenic analysis shows H3 tail residues 11-27 to be the sole binding segment for Impβ, Kapβ2, and Imp4. However, Imp5, Imp7, Imp9, and Impα bind two separate elements in the H3 tail: the segment at residues 11-27 and an isoleucine-lysine nuclear localization signal (IK-NLS) motif at residues 35-40. The H4 tail also uses either one or two basic segments to bind the same set of Importins with a similar trend of relative affinities as the H3 tail, albeit at least 10-fold weaker. Of the many lysine residues in the H3 and H4 tails, only acetylation of the H3 Lys14substantially decreased binding to several Importins. Lastly, we show that, in addition to the N-terminal tails, the histone fold domains of H3 and H4 and/or the histone chaperone Asf1b are important for Importin-histone recognition.
authors.affiliation: From the Department of Pharmacology, University of Texas Southwestern, Dallas, Texas 75390.
authors.forename: Michael
authors.initials: M
authors.lastname: Soniat
authors.affiliation: From the Department of Pharmacology, University of Texas Southwestern, Dallas, Texas 75390.
authors.forename: Tolga
authors.initials: T
authors.lastname: Cağatay
authors.affiliation: From the Department of Pharmacology, University of Texas Southwestern, Dallas, Texas 75390 yuhmin.chook@utsouthwestern.edu.
authors.forename: Yuh Min
authors.initials: YM
authors.lastname: Chook
mesh_terms: D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D028884:Karyopherins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016296:Mutagenesis; D011485:Protein Binding; D000072417:Protein Domains
chemical_list: C491640:ASF1B protein, human; D018797:Cell Cycle Proteins; D006657:Histones; D028884:Karyopherins; D018832:Molecular Chaperones
keywords: chromatin regulation; histone; histone acetylation; importin; karyopherin; nuclear import; nuclear localization signal; nuclear transport; protein import