title: The methyl-CpG binding protein MBD1 interacts with the p150 subunit of chromatin assembly factor 1.
abstract: DNA promoter hypermethylation has been shown to be a functional mechanism of transcriptional repression. This epigenetic gene silencing is thought to involve the recruitment of chromatin-remodeling factors, such as histone deacetylases, to methylated DNA via a family of proteins called methyl-CpG binding proteins (MBD1 to -4). MBD1, a member of this family, exhibits transcription-repressive activity, but to this point no interacting protein partners have been identified. In this study, we demonstrate that MBD1 partners with the p150 subunit of chromatin assembly factor 1 (CAF-1), forming a multiprotein complex that also contains HP1alpha. The MBD1-CAF-1 p150 interaction requires the methyl-CpG binding domain of MBD1, and the association occurs in the C terminus of CAF-1 p150. The two proteins colocalize to regions of dense heterochromatin in mouse cells, and overexpression of the C terminus of CAF-1 p150 prevents the targeting of MBD1 in these cells without disrupting global heterochromatin structure. This interaction suggests a role for MBD1 and CAF-1 p150 in methylation-mediated transcriptional repression and the inheritance of epigenetically determined chromatin states.
authors.affiliation: Tumor Biology Division, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Reese
authors.forename: Kurtis E
authors.initials: KE
authors.lastname: Bachman
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Baylin
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rountree
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D056504:Chromatin Assembly Factor-1; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008322:Mammals; D051379:Mice; D046912:Multiprotein Complexes; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: C000715594:CBX5 protein, human; C533593:CHAF1B protein, human; C489780:CNOT8 protein, human; D002352:Carrier Proteins; C533592:Chaf1a protein, mouse; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006570:Heterochromatin; C066141:MBD1 protein, human; D046911:Macromolecular Substances; C489323:Mbd1 protein, mouse; D046912:Multiprotein Complexes; D012097:Repressor Proteins; D014157:Transcription Factors; D000090266:Chromobox Protein Homolog 5