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

Takeshi Sekiya, Kensaku Murano, Kohsuke Kato, Atsushi Kawaguchi, Kyosuke Nagata

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)397-404
Number of pages8
JournalFEBS Open Bio
Volume7
Issue number3
DOIs
Publication statusPublished - 2017 Mar 1

Fingerprint

Phosphorylation
Mitosis
Chromatin
Chromosomes
Zinc
DNA
Chromosome Structures
Chromosome Segregation
Zinc Fingers
Data storage equipment
Amino Acids
Epigenomics
CCCTC-binding factor
Proteins
Mutation

Keywords

  • higher order chromatin structure
  • mitosis
  • zinc finger protein

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mitotic phosphorylation of CCCTC-binding factor (CTCF) reduces its DNA binding activity. / Sekiya, Takeshi; Murano, Kensaku; Kato, Kohsuke; Kawaguchi, Atsushi; Nagata, Kyosuke.

In: FEBS Open Bio, Vol. 7, No. 3, 01.03.2017, p. 397-404.

Research output: Contribution to journalArticle

Sekiya, Takeshi ; Murano, Kensaku ; Kato, Kohsuke ; Kawaguchi, Atsushi ; Nagata, Kyosuke. / Mitotic phosphorylation of CCCTC-binding factor (CTCF) reduces its DNA binding activity. In: FEBS Open Bio. 2017 ; Vol. 7, No. 3. pp. 397-404.
@article{5e6900e1bb884ae289eb54a6d84908d4,
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 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.",
keywords = "higher order chromatin structure, mitosis, zinc finger protein",
author = "Takeshi Sekiya and Kensaku Murano and Kohsuke Kato and Atsushi Kawaguchi and Kyosuke Nagata",
year = "2017",
month = "3",
day = "1",
doi = "10.1002/2211-5463.12189",
language = "English",
volume = "7",
pages = "397--404",
journal = "FEBS Open Bio",
issn = "2211-5463",
publisher = "Elsevier BV",
number = "3",

}

TY - JOUR

T1 - Mitotic phosphorylation of CCCTC-binding factor (CTCF) reduces its DNA binding activity

AU - Sekiya, Takeshi

AU - Murano, Kensaku

AU - Kato, Kohsuke

AU - Kawaguchi, Atsushi

AU - Nagata, Kyosuke

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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.

AB - 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.

KW - higher order chromatin structure

KW - mitosis

KW - zinc finger protein

UR - http://www.scopus.com/inward/record.url?scp=85014521099&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014521099&partnerID=8YFLogxK

U2 - 10.1002/2211-5463.12189

DO - 10.1002/2211-5463.12189

M3 - Article

AN - SCOPUS:85014521099

VL - 7

SP - 397

EP - 404

JO - FEBS Open Bio

JF - FEBS Open Bio

SN - 2211-5463

IS - 3

ER -