Characterisation of nuclear localisation signals of the four human core histones.
The four core histones H2A, H2B, H3 and H4 are transported from the cytoplasm into the nucleus by a receptor-mediated and energy-dependent process. This nuclear transport depends on topogenic signals in the individual histone protein sequences. We have analysed such nuclear localisation signals in the core histones by means of fusion proteins consisting of individual core histones (or fragments thereof) and beta-galactosidase as a reporter protein. The results show that each of the four core histones contains several portions that are capable of mediating nuclear transport. One type of topogenic sequences consists of clustered basic amino acids in the amino terminal segments of each of the core histones. The globular portions of the core histones represent a second type of nuclear localisation signals that could only mediate nuclear transport when the whole protein domains were fused to the beta-galactosidase reporter. Fragments of the globular domains derived from each of the four core histones could not serve as nuclear localisation signals. We conclude that the nuclear targeting of core histones requires information conferred by the globular domain conformation.
Institute of Biochemistry, Department of Molecular Biology, University of Goettingen, D-37073 Goettingen, Germany.
M
M
Baake
D
D
Doenecke
W
W
Albig
D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D019913:Nuclear Localization Signals / Q000737:chemistry*; D010957:Plasmids / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism
D006657:Histones; D019913:Nuclear Localization Signals; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase