A common mode of recognition for methylated CpG.
Much is known about vertebrate DNA methylation, however it is not known how methylated CpG within particular sequences is recognized. Two recent structures of C2H2 zinc finger (ZnF) proteins in complex with methylated DNA reveal a common recognition mode for 5-methylcytosine (5mC) that involves a 5mC-Arg-G triad. In the two ZnF proteins, an arginine that precedes the first Zn-binding histidine (RH motif) can interact with a 5mCpG or TpG dinucleotide. Among a family of >300 human Krüppel-associated box (KRAB) domain containing ZnF proteins examined, two-thirds contained at least one ZnF that included an RH motif. We propose that the RH-ZnF motifs provide specificity for 5mCpG, whereas the neighboring Zn fingers recognize the surrounding DNA sequence context.
Departments of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
Yiwei
Y
Liu
Xing
X
Zhang
Robert M
RM
Blumenthal
Xiaodong
X
Cheng
D001483:Base Sequence; D017124:Conserved Sequence; D018899:CpG Islands; D003596:Cytosine / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C422407:ZNF350 protein, human; C118822:Zbtb33 protein, mouse; D003596:Cytosine