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Mitotic phosphorylation of CCCTC-binding factor (CTCF) reduces its DNA binding activity
Takeshi Sekiya1, Kensaku Murano2, Kohsuke Kato3
1Department of Infection Biology Faculty of Medicine and Graduate School of Comprehensive Human Science University of Tsukuba Japan.
FEBS Open Bio
|March 14, 2017
Summary
Mitotic phosphorylation of linker domains in CCCTC-binding factor (CTCF) reduces its DNA-binding activity. This phosphorylation is crucial for CTCF
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- CCCTC-binding factor (CTCF) is vital for chromatin architecture and epigenetic memory.
- Its role and regulation during mitosis remain largely unknown.
- Accurate chromosome segregation during mitosis requires dynamic chromatin remodeling.
Purpose of the Study:
- To investigate the regulatory mechanisms of CTCF during mitosis.
- To determine how CTCF's DNA-binding activity is modulated in mitotic cells.
Main Methods:
- Phosphorylation site analysis of CTCF during mitosis.
- In vitro DNA-binding assays.
- Site-directed mutagenesis of identified phosphorylation residues.
Main Results:
- CTCF DNA-binding activity is regulated by phosphorylation during mitosis.
- Specific linker domains within the CTCF zinc finger domain are phosphorylated.
- Mitotic phosphorylation of linker domains impairs CTCF's in vitro DNA-binding capacity.
- Identified phosphorylation sites include Thr289, Thr317, Thr346, Thr374, Ser402, Ser461, and Thr518.
Conclusions:
- Mitotic phosphorylation of CTCF linker domains is essential for its dissociation from mitotic chromatin.
- This phosphorylation-dependent regulation ensures proper chromosome segregation during cell division.
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