title: Pathways mediating the nuclear import of histones H3 and H4 in yeast.
abstract: The correct assembly of chromatin is necessary for the maintenance of genomic stability in eukaryotic cells. A critical step in the assembly of new chromatin is the cell cycle-regulated synthesis and nuclear import of core histones. Here we demonstrate that the nuclear import pathway of histones H3 and H4 is mediated by at least two karyopherins/importins, Kap123p and Kap121p. Cytosolic H4 is found associated with Kap123p and H3. Kap121p is also present in the H4-PrA-associated fractions, albeit in lesser amounts than Kap123p, suggesting that this Kap serves as an additional import receptor. We further demonstrate that cytosolic Kap123p is associated with acetylated H3 and H4. H3 and H4 each contain a nuclear localization signal (NLS) in their amino-terminal domains. These amino-terminal domains were found to be essential for the nuclear accumulation of H3 and H4-green fluorescent protein reporters. Each NLS mediated direct binding to Kap123p and Kap121p, and decreased nuclear accumulation of H3 and H4 NLS-green fluorescent protein reporters was observed in specific kap mutant strains. H3 and H4 are the first histones to be assembled onto DNA, and these results show that their import is mediated by at least two import pathways.
authors.affiliation: Center for Cell Signaling, Department of Microbiology, University of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Nima
authors.initials: N
authors.lastname: Mosammaparast
authors.forename: Yurong
authors.initials: Y
authors.lastname: Guo
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Shabanowitz
authors.forename: Donald F
authors.initials: DF
authors.lastname: Hunt
authors.forename: Lucy F
authors.initials: LF
authors.lastname: Pemberton
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D051548:Histone Acetyltransferases; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015003:Yeasts / Q000378:metabolism*; D028961:beta Karyopherins
chemical_list: D006657:Histones; C400425:KAP114 protein, S cerevisiae; D026901:Membrane Transport Proteins; D009687:Nuclear Proteins; C483822:PSE1 protein, S cerevisiae; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D028961:beta Karyopherins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases