Importin α2 association with chromatin: Direct DNA binding via a novel DNA binding domain

Abstract

AbstractNuclear transport of proteins is important for facilitating appropriate nuclear functions. The proteins of the importin α family play key roles in nuclear transport as transport receptors for a huge number of nuclear proteins. Additionally, these proteins possess other functions, including chromatin association and gene regulation. However, these non-transport functions of importin α are not yet fully understood, especially their molecular-level mechanisms for functioning with chromatin and their consequences. Here, we report the novel molecular characteristics of importin α involving binding to diverse 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 α within the conventional importin β binding (IBB) domain, which was shown to be necessary for nuclear transport of cargo proteins. We propose a ‘stroll and locate’ model to explain the association of importin α with chromatin. This is the first study to delineate the interaction between importin α and chromatin DNA via the NAAT domain, indicating the bifunctionality of the importin α N-terminal region for nuclear transport and chromatin association.