Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs

• Published in: Cell Vol. 58; no. 3; pp. 499 - 507
• Main Authors: Meehan, Richard R., Lewis, Joe D., McKay, Stewart, Kleiner, Elke L., Bird, Adrian P.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 11.08.1989; Cell Press
• Subjects: 5-Methylcytosine; Analytical, structural and metabolic biochemistry; Binding and carrier proteins; Binding, Competitive; Biological and medical sciences; Cell Line; Cell Nucleus - analysis; Cytosine - analogs & derivatives; Cytosine - metabolism; DNA (Cytosine-5-)-Methyltransferases - metabolism; DNA - metabolism; DNA Probes; DNA-Binding Proteins - isolation & purification; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Humans; Methylation; Molecular Weight; Proteins; Structure-Activity Relationship; Vertebrata; Characterization; Vertebrata; Mammalia; Gel electrophoresis; DNA binding protein; Gel filtration; Molecular interaction; Molecular probe; Methylation
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(89)90430-3

The effects of DNA methylation on transcription and chromatin structure require that nuclear factors be able to distinguish methylated and nonmethylated DNA. We describe a methyl-CpG binding protein (MeCP) that complexes with a variety of unrelated DNA sequences when they are methylated at CpG. Fifteen or more symmetrically methylated CpG moieties per molecule are required for strong binding under our conditions. Competition experiments show that vertebrate DNAs bind to MeCP, whereas naturally nonmethylated genomes or cloned vertebrate genomes do not bind. Cross-linking experiments detect a 120 kd protein that correlates stringently with MeCP activity. Species and tissue comparisons show that MeCP is widely distributed in mammals except in embryonal carcinoma cell lines, which have very low levels.