Structure-specific binding of MeCP2 to four-way junction DNA through its methyl CpG-binding domain.
MeCP2, whose methylated DNA-binding domain (MBD) binds preferentially to DNA containing 5Me-CpG relative to linear unmethylated DNA, also binds preferentially, and with similar affinity, to unmethylated four-way DNA junctions through the MBD. The Arg133Cys (R133C) mutation in the MBD, a Rett syndrome mutation that abolishes binding to methylated DNA, leads to only a slight reduction in the affinity of the MBD for four-way junctions, suggesting distinct but partially overlapping modes of binding to junction and methylated DNA. Binding to unmethylated DNA junctions is likely to involve a subset of the interactions that occur with methylated DNA. High-affinity, methylation-independent binding to four-way junctions is consistent with additional roles for MeCP2 in chromatin, beyond recognition of 5Me-CpG.
Galvão
Teca Calcagno
TC
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK.
Thomas
Jean O
JO
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018899:CpG Islands; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D019175:DNA Methylation; D051783:Methyl-CpG-Binding Protein 2 / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D051381:Rats
C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2; D004247:DNA