title: Mitotic phosphorylation of CCCTC-binding factor (CTCF) reduces its DNA binding activity.
abstract: During mitosis, higher order chromatin structures are disrupted and chromosomes are condensed to achieve accurate chromosome segregation. CCCTC-binding factor (CTCF) is a highly conserved and ubiquitously expressed C2H2-type zinc finger protein which is considered to be involved in epigenetic memory through regulation of higher order chromatin architecture. However, the regulatory mechanism of CTCF in mitosis is still unclear. Here we found that the DNA-binding activity of CTCF is regulated in a phosphorylation-dependent manner during mitosis. The linker domains of the CTCF zinc finger domain were found to be phosphorylated during mitosis. The phosphorylation of linker domains impaired the DNA-binding activityin vitro. Mutation analyses showed that amino acid residues (Thr289, Thr317, Thr346, Thr374, Ser402, Ser461, and Thr518) located in the linker domains were phosphorylated during mitosis. Based on these results, we propose that the mitotic phosphorylation of the linker domains of CTCF is important for the dissociation of CTCF from mitotic chromatin.
authors.affiliation: Department of Infection Biology Faculty of Medicine and Graduate School of Comprehensive Human Science University of Tsukuba Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sekiya
authors.affiliation: Department of Molecular Biology Keio University School of Medicine Tokyo Japan.
authors.forename: Kensaku
authors.initials: K
authors.lastname: Murano
authors.affiliation: Department of Infection BiologyFaculty of Medicine and Graduate School of Comprehensive Human ScienceUniversity of TsukubaJapan; Faculty of MedicineUniversity of TsukubaJapan.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Infection BiologyFaculty of Medicine and Graduate School of Comprehensive Human ScienceUniversity of TsukubaJapan; Faculty of MedicineUniversity of TsukubaJapan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawaguchi
authors.affiliation: Faculty of Medicine University of Tsukuba Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Nagata
keywords: higher order chromatin structure; mitosis; zinc finger protein