Importin alpha 2 association with chromatin: Direct DNA binding via a novel DNA-binding domain

The nuclear transport of proteins is important for facilitating appropriate nuclear functions. The importin alpha family proteins play key roles in nuclear transport as transport receptors for copious nuclear proteins. Additionally, these proteins possess other functions, including chromatin association and gene regulation. However, these nontransport functions of importin alpha are not yet fully understood, especially their molecular-level mechanisms and consequences for functioning with chromatin. Here, we report the novel molecular characteristics of importin alpha binding to diverse DNA sequences in chromatin. We newly identified and characterized a DNA-binding domain-the Nucleic Acid Associating Trolley pole domain (NAAT domain)-in the N-terminal region of importin alpha within the conventional importin beta binding (IBB) domain that is necessary for nuclear transport of cargo proteins. Furthermore, we found that the DNA binding of importin alpha synergistically coupled the recruitment of its cargo protein to DNA. This is the first study to delineate the interaction between importin alpha and chromatin DNA via the NAAT domain, indicating the bifunctionality of the importin alpha N-terminal region for nuclear transport and chromatin association.