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MBD5 and MBD6 interact with the human PR-DUB complex through their methyl-CpG-binding domain
H Irem Baymaz1, Alexandra Fournier, Sophie Laget
1Molecular Cancer Research, Cancer Genomics, University Medical Center Utrecht, Utrecht, The Netherlands.
Methyl-CpG-binding domain (MBD) proteins MBD5 and MBD6 interact with the PR-DUB complex. MBD6 is recruited to DNA damage sites, suggesting distinct roles for these MBD proteins.
Area of Science:
- Molecular Biology
- Epigenetics
- Protein Interactions
Background:
- Methyl-CpG-binding domain (MBD) proteins MBD5 and MBD6 are poorly understood.
- Previous studies did not demonstrate MBD5/MBD6 MBD binding to methylated DNA.
Purpose of the Study:
- To investigate the function and interactions of MBD5 and MBD6.
- To elucidate the role of the MBD domain in MBD5/MBD6 interactions.
Main Methods:
- Protein interaction assays.
- Mammalian PR-DUB Polycomb complex analysis.
- Chromatin immunoprecipitation (ChIP).
Main Results:
- MBD5 and MBD6 bind the PR-DUB complex mutually exclusively.
- The MBD of MBD5 and MBD6 is essential and sufficient for PR-DUB interaction.
- MBD6 and FOXK2/PR-DUB share genomic targets.
- MBD6, unlike MBD5, is recruited to DNA damage sites independently of PR-DUB.
Conclusions:
- MBD5 and MBD6 share a function via PR-DUB interaction.
- MBD6 has a specific role in DNA damage response.
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