4.3 Article

Mitotic phosphorylation of CCCTC-binding factor (CTCF) reduces its DNA binding activity

Journal

FEBS OPEN BIO
Volume 7, Issue 3, Pages 397-404

Publisher

WILEY
DOI: 10.1002/2211-5463.12189

Keywords

higher order chromatin structure; mitosis; zinc finger protein

Funding

  1. Ministry of Education, Culture, Sports, Science, and Technology of Japan [16H05192, 24115002]
  2. Grants-in-Aid for Scientific Research [16H05192, 24115002] Funding Source: KAKEN

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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 activity in 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.

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