Phosphorylation-mediated disassembly of C-terminal binding protein 2 tetramer impedes epigenetic silencing of pluripotency in mouse embryonic stem cells
2024

How DNA Damage Affects Stem Cell Function

publication 10 minutes Evidence: high

Author Information

Author(s): Lee Han-Teo, Kim Young Ah, Lee Sangho, Jung Ye-Eun, Kim Hanbyeol, Kim Tae Wan, Kwak Sojung, Kim Jaehyeon, Lee Chul-Hwan, Cha Sun-Shin, Choi Jinmi, Cho Eun-Jung, Youn Hong-Duk

Primary Institution: Seoul National University College of Medicine

Hypothesis

How does DNA damage influence the function of C-terminal binding protein 2 (Ctbp2) in mouse embryonic stem cells?

Conclusion

Phosphorylation of Ctbp2 during DNA damage disrupts its tetramer formation, leading to reduced binding to chromatin and altered gene expression.

Supporting Evidence

  • Phosphorylation of Ctbp2 at serine 164 is crucial for its function.
  • Chk2 is identified as the key kinase that phosphorylates Ctbp2 in response to DNA damage.
  • Phosphorylated Ctbp2 shows increased binding to PRC2, altering its role in gene regulation.
  • DNA damage leads to the dissociation of Ctbp2 from chromatin, affecting pluripotency gene expression.

Takeaway

When stem cells get hurt, a protein called Ctbp2 changes shape and can't hold onto DNA as well, which helps the cells stay healthy.

Methodology

The study used mouse embryonic stem cells and various assays including immunoprecipitation, chromatin immunoprecipitation, and in vitro phosphorylation assays to investigate the role of Ctbp2.

Limitations

The study primarily focuses on mouse embryonic stem cells, which may not fully represent human stem cell behavior.

Participant Demographics

Mouse embryonic stem cells were used in the study.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1093/nar/gkae1076

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