MBD5 and MBD6 interact with the human PR-DUB complex through their methyl-CpG binding domain — Vermeulen and collaborator labs (2014)
Thursday, April 24, 2014
H. Irem Baymaz et al. (Michiel Vermeulen)
MBD5 and MBD6 are two members of the methyl-CpG binding domain (MBD) family of proteins that are poorly characterized. Studies performed thus far have failed to show binding of the MBD5 and MBD6 MBD domain to methylated DNA. Here, we show that both MBD5 and MBD6 interact with the mammalian PR-DUB Polycomb protein complex in a mutually exclusive manner. Strikingly, the MBD domain of MBD5 and MBD6 is both necessary and sufficient to mediate this interaction. ChIP analyses reveal that MBD6 and FOXK2/PR-DUB share a subset of genomic target genes, suggesting a functional interaction in vivo. Finally, we show that MBD6, but not MBD5, gets recruited to sites of DNA damage in a PR-DUB
independent manner. Our study thus implies a shared function for MBD5 and MBD6 through an interaction with PR-DUB, as well as an MBD6-specific recruitment to sites of DNA damage.
Proteomics (2014) 14: 2179-2189 doi: 10.1002/pmic.201400013