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

• Published in: Genes to cells : devoted to molecular & cellular mechanisms 2021-12, Vol.26 (12), p.945-966
• Main Authors: Jibiki, Kazuya, Kodama, Takashi S., Suenaga, Atsushi, Kawase, Yota, Shibazaki, Noriko, Nomoto, Shin, Nagasawa, Seiya, Nagashima, Misaki, Shimodan, Shieri, Kikuchi, Renan, Okayasu, Mina, Takashita, Ruka, Mehmood, Rashid, Saitoh, Noriko, Yoneda, Yoshihiro, Akagi, Ken‐ichi, Yasuhara, Noriko
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus; alpha Karyopherins - genetics; alpha Karyopherins - metabolism; Cell Nucleus - metabolism; Chromatin; Chromatin - metabolism; Deoxyribonucleic acid; DNA; DNA‐binding protein; Gene regulation; importin α; Nuclear Localization Signals - metabolism; Nuclear Proteins - metabolism; Nuclear transport; Nucleotide sequence; nucleus; Protein Binding; Protein transport; Proteins; protein−DNA interaction; α‐helix
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/gtc.12896

The nuclear transport of proteins is important for facilitating appropriate nuclear functions. The importin α 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 α 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 α 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 α within the conventional importin β binding (IBB) domain that is necessary for nuclear transport of cargo proteins. Furthermore, we found that the DNA binding of importin α synergistically coupled the recruitment of its cargo protein to DNA. 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. This is the first study to delineate the interaction between importin alpha and DNA via the novel DNA binding domain, indicating the bifunctionality of the importin alpha N‐terminal region for nuclear transport and chromatin association.