The first step in the assembly of new chromatin is the cell cycle-regulated 
synthesis and nuclear import of core histones. The core histones include H2A and 
H2B, which are assembled into nucleosomes as heterodimers. We show here that the 
import of histone H2A and H2B is mediated by several members of the karyopherin 
(Kap; importin) family. An abundant complex of H2A, H2B, and Kap114p was 
detected in cytosol. In addition, two other Kaps, Kap121p and Kap123p, and the 
histone chaperone Nap1p were isolated with H2A and H2B. Nap1p is not necessary 
for the formation of the Kap114p-H2A/H2B complex or for import of H2A and H2B. 
We demonstrate that both histones contain a nuclear localization sequence (NLS) 
in the amino-terminal tail. Fusions of the NLSs to green fluorescent protein 
were specifically mislocalized to the cytoplasm in kap mutant strains. In 
addition, we detected a specific mislocalization in a kap95 
temperature-sensitive strain, suggesting that this Kap is also involved in the 
import of H2A and H2B in vivo. Importantly, we show that Kap114p, Kap121p, and 
Kap95 interact directly with both histone NLSs and that RanGTP inhibits this 
association. These data suggest that the import of H2A and H2B is mediated by a 
network of Kaps, in which Kap114p may play the major role.