title: MBD5 and MBD6 interact with the human PR-DUB complex through their methyl-CpG-binding domain.
abstract: 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 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 of MBD5 and MBD6 is both necessary and sufficient to mediate this interaction. Chromatin immunoprecipitation 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, is 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.
authors.affiliation: Molecular Cancer Research, Cancer Genomics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: H Irem
authors.initials: HI
authors.lastname: Baymaz
authors.forename: Alexandra
authors.initials: A
authors.lastname: Fournier
authors.forename: Sophie
authors.initials: S
authors.lastname: Laget
authors.forename: Zongling
authors.initials: Z
authors.lastname: Ji
authors.forename: Pascal W T C
authors.initials: PW
authors.lastname: Jansen
authors.forename: Arne H
authors.initials: AH
authors.lastname: Smits
authors.forename: Laure
authors.initials: L
authors.lastname: Ferry
authors.forename: Anneloes
authors.initials: A
authors.lastname: Mensinga
authors.forename: Ina
authors.initials: I
authors.lastname: Poser
authors.forename: Andrew
authors.initials: A
authors.lastname: Sharrocks
authors.forename: Pierre-Antoine
authors.initials: PA
authors.lastname: Defossez
authors.forename: Michiel
authors.initials: M
authors.lastname: Vermeulen
mesh_terms: D000595:Amino Acid Sequence; D002843:Chromatin; D004249:DNA Damage; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D063146:Polycomb-Group Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: C400134:BAP1 protein, human; D002843:Chromatin; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C550332:MBD5 protein, human; C553236:MBD6 protein, human; D063146:Polycomb-Group Proteins; D025521:Tumor Suppressor Proteins; C070635:interleukin binding factor; D043222:Ubiquitin Thiolesterase
keywords: Cell biology; Chromatin; Protein-protein interactions