Multiple pathways contribute to nuclear import of core histones

Nuclear import of the four core histones H2A, H2B, H3 and H4 is one of the main nuclear import activities during S-phase of the cell cycle. However, t he molecular machinery facilitating nuclear import of core histones has not been elucidated. Here, we investigated the pathways by which histone impor t can occur. First, we show that core histone import can be competed by the BIB (beta -like import receptor binding) domain of ribosomal protein L23a suggesting that histone import is an importin mediated process. Secondly, a ffinity chromatography on immobilized core histones revealed that several m embers of the importin beta family of transport receptors are able to inter act with core histones. Finally, we demonstrate that at least four known an d one novel importin, importin 9, can mediate nuclear import of core histon es into the nuclei of permeabilized cells. Our results suggest that multipl e pathways of import exist to provide efficient nuclear uptake of these abu ndant, essential proteins.