The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Molecular basis for recognition of methylated and specific DNA sequences by the zinc finger protein Kaiso
Open accessAbstract
Methylation of CpG dinucleotides in DNA is a common epigenetic modification in eukaryotes that plays a central role in maintenance of genome stability, gene silencing, genomic imprinting, development, and disease. Kaiso, a bifunctional Cys 2 His 2 zinc finger protein implicated in tumor-cell proliferation, binds to both methylated CpG (mCpG) sites and a specific nonmethylated DNA motif (TCCTGCNA) and represses transcription by recruiting chromatin remodeling corepression machinery to target genes. Here we report structures of the Kaiso zinc finger DNA-binding domain in complex with its nonmethylated, sequence-specific DNA target (KBS) and with a symmetrically methylated DNA sequence derived from the promoter region of E-cadherin . Recognition of specific bases in the major groove of the core KBS and mCpG sites is accomplished through both classical and methyl CH···O hydrogen-bonding interactions with residues in the first two zinc fingers, whereas residues in the C-terminal extension following the third zinc finger bind in the opposing minor groove and are required for high-affinity binding. The C-terminal region is disordered in the free protein and adopts an ordered structure upon binding to DNA. The structures of these Kaiso complexes provide insights into the mechanism by which a zinc finger protein can recognize mCpG sites as well as a specific, nonmethylated regulatory DNA sequence.
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“the presence of a bulky methyl group in the major groove leads to a subtle widening of the major groove and a subtle narrowing of the minor groove.”
From Transcription factors as readers and effectors of DNA methylation (2016) · cites this paper as [72]
In the citing paper
“Zinc finger protein 681 contains a classical C 2 H 2 (Kruppel) zinc finger motif and functions as an activator and repressor of transcription, regulating proliferation, differentiation, and development.38,49”
From Altered genome-wide methylation in endometriosis (2014) · cites this paper as [49]
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Metadata
- Authors
- Buck-Koehntop, B. A., Stanfield, R. L., Ekiert, D. C., Martinez-Yamout, M. A., Dyson, H. J., Wilson, I. A., & Wright, P. E.
- Affiliations
- Department of Molecular Biology and
- Scripps Research Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-09-04
- Volume
- 109
- Issue
- 38
- Pages
- 15229-15234
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3458336
- OpenAlex
- W2021958912
- Cited by
- 128
- References
- 36
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 11 · 2023: 5 · 2022: 15 · 2021: 8 · 2020: 6 · 2019: 5 · 2018: 10 · 2017: 8 · 2016: 13 · 2015: 11 · 2014: 12 · 2013: 10
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (Y1-CO-1020)
- National Institute of General Medical Sciences (R01GM036643, Y1-GM-1104, GM036643)
- National Center for Research Resources (P41RR001209)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- Kaiso, C2H2 zinc finger, DNA methylation, CpG, sequence-specific DNA recognition, transcriptional repression, E-cadherin promoter, C-terminal extension, protein-DNA complex
- MeSH terms
- Base Sequence, Chromatin, DNA, Humans, Hydrogen-Ion Concentration, Molecular Conformation, Molecular Sequence Data, Magnetic Resonance Spectroscopy, Promoter Regions, Genetic, Protein Binding, Transcription Factors, Cadherins, Zinc Fingers, Protein Structure, Tertiary, Protein Folding, Crystallography, X-Ray, CpG Islands, DNA Methylation
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