The Structural Basis for Selective Binding of Non-methylated CpG Islands by the CFP1 CXXC Domain

Overview

Journal Nat Commun

Specialty Biology

Date 2011 Mar 17

PMID 21407193

Citations 67

Authors

Chao Xu

Chuanbing Bian

Robert Lam

Aiping Dong

Jinrong Min

Affiliations

Soon will be listed here.

Abstract

CFP1 is a CXXC domain-containing protein and an essential component of the SETD1 histone H3K4 methyltransferase complex. CXXC domain proteins direct different chromatin-modifying activities to various chromatin regions. Here, we report crystal structures of the CFP1 CXXC domain in complex with six different CpG DNA sequences. The crescent-shaped CFP1 CXXC domain is wedged into the major groove of the CpG DNA, distorting the B-form DNA, and interacts extensively with the major groove of the DNA. The structures elucidate the molecular mechanism of the non-methylated CpG-binding specificity of the CFP1 CXXC domain. The CpG motif is confined by a tripeptide located in a rigid loop, which only allows the accommodation of the non-methylated CpG dinucleotide. Furthermore, we demonstrate that CFP1 has a preference for a guanosine nucleotide following the CpG motif.

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