title: MBD4 interacts with and recruits USP7 to heterochromatic foci.
abstract: MBD4 is the only methyl-CpG binding protein that possesses a C-terminal glycosylase domain. It has been associated with a number of nuclear pathways including DNA repair, DNA damage response, the initiation of apoptosis, transcriptional repression, and DNA demethylation. However, the precise contribution of MBD4 to these processes in development and relevant diseases remains elusive. We identified UHRF1 and USP7 as two new interaction partners for MBD4. Both UHRF1, a E3 ubiquitin ligase, and USP7, a de-ubiquinating enzyme, regulate the stability of the DNA maintenance methyltransferase, Dnmt1. The ability of MBD4 to directly interact with and recruit USP7 to chromocenters implicates it as an additional factor that can potentially regulate Dnmt1 activity during cell proliferation.
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK; Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Meng
authors.forename: David J
authors.initials: DJ
authors.lastname: Harrison
authors.forename: Richard R
authors.initials: RR
authors.lastname: Meehan
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D004261:DNA Replication; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006570:Heterochromatin / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011485:Protein Binding; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D000076084:Ubiquitin-Specific Peptidase 7
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D006570:Heterochromatin; D049452:Green Fluorescent Proteins; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases; D004706:Endodeoxyribonucleases; C118712:MBD4 protein, human; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7
keywords: HETEROCHROMATIN REPLICATION AND FORMATION; MBD4; UHRF1; USP7