中山計画研究代表による成果がFASEB Journal誌に掲載されました!
Mitotic Phosphorylation of Swi6/HP1 Regulates Its Chromatin Binding and Chromosome Segregation
Yuriko Yoshimura, Aki Hayashi, Mayo Tanaka, Mieko Suzuki-Matsubara, Reiko Nakagawa, Gohei Nishibuchi, Hideaki Tagami, Masaya Oki, Jun-ichi Nakayama
Abstract
In eukaryotic cells, heterochromatin assembly is critical for chromosome segregation and transcriptional gene silencing. Heterochromatin protein 1 (HP1) is a conserved chromosomal protein that plays an important role in heterochromatin assembly. We have previously shown that mammalian HP1α and Schizosaccharomyces pombe Swi6 are phosphorylated by casein kinase II (CK2) and that this phosphorylation is essential for their function in heterochromatin assembly. In addition to CK2-mediated phosphorylation, several studies have shown that HP1 proteins undergo additional phosphorylation during mitosis. However, functional significance of the mitotic phosphorylation of HP1 remains unclear. Here, we identified mitotic phosphorylation sites within fission yeast Swi6 and showed that this phosphorylation is involved in chromosome segregation. Using an Escherichia coli co-expression system, we showed that Swi6 is phosphorylated by Ark1, a solo Aurora kinase in S. pombe, and mutational analyses revealed that serine residues in the conserved N-terminal region of Swi6 are the primary targets of Ark1. By expressing mutant Swi6, we confirmed that these serine residues are phosphorylated during mitosis in vivo. Although non-phosphorylatable or phosphomimic mutations in Swi6 had little effect on heterochromatic silencing, they caused defects in early chromosome segregation and modulated the temperature-sensitive growth of mutant cells for chromosome passenger complex components. These results suggest that the Ark1-mediated mitotic phosphorylation of Swi6 is involved in chromosome segregation during mitosis and implicates a conserved regulatory role for the mitotic phosphorylation of HP1 proteins.
FASEB Journal, doi: 10.1096/fj.202500384R. (2025)
https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202500384R
