The structural basis for selective binding of non-methylated CpG islands by the CFP1 CXXC domain
Open accessAbstract
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. CXXC domain proteins bind to CpG DNA sequences and influence chromatin modification. Xuet al.report crystal structures of the CXXC protein CFP1, a component of the SETD1 histone H3K4 methyl transferase complex, and study the molecular mechanisms of DNA-binding specificity.
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The Asn-Gua residue base pairing is analogous to the Arg-Gua pair in DNA-bound CXXC domain structures.
“The Asn-Gua residue base pairing is analogous to the Arg-Gua pair in the DNA-bound CXXC domain structures (9, 21).”
From Structural studies of SALL family protein zinc finger cluster domains in complex with DNA reveal preferential binding to an AATA tetranucleotide motif (2022) · cites this paper as [9]
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- Authors
- Xu, C., Bian, C., Lam, R., Dong, A., & Min, J.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Min, Jinrong
- Venue
- Nature Communications
- Published
- 2011-03-08
- Volume
- 2
- Issue
- 1
- Pages
- 227-227
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC3072069
- OpenAlex
- W2037374227
- Cited by
- 130
- References
- 35
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 3 · 2023: 2 · 2022: 15 · 2021: 7 · 2020: 9 · 2019: 4 · 2018: 9 · 2017: 12 · 2016: 5 · 2015: 11 · 2014: 10 · 2013: 14 · 2012: 13
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- GlaxoSmithKline
- Ontario Innovation Trust
- Genome Canada (1097737)
- Wellcome Trust (1097737)
- Ontario Genomics
- Ontario Genomics Institute
- Stiftelsen för Strategisk Forskning
- Karolinska Institutet
- Knut och Alice Wallenbergs Stiftelse
- Canadian Institutes of Health Research (1097737)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- CFP1, CXXC domain, CpG islands, DNA binding specificity, DNA major groove, crystal structure, chromatin modification
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Cell Nucleus, Chromatin, Cloning, Molecular, Crystallization, DNA, DNA-Binding Proteins, Escherichia coli, Histones, Humans, Models, Molecular, Molecular Sequence Data, Oligopeptides, Protein Binding, Recombinant Proteins, Structure-Activity Relationship, Trans-Activators, Sequence Alignment, Protein Structure, Tertiary, Crystallography, X-Ray, CpG Islands, DNA Methylation
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