ArticleBiochemistry2018
CH···O Hydrogen Bonds Mediate Highly Specific Recognition of Methylated CpG Sites by the Zinc Finger Protein Kaiso.
Article in Biochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Review
- Kaiso reads methylated CpGs at nucleosome entry/exit and displaces the H3 tail.bioRxiv : the preprint server for biology · 2026Article
- Article
- Dissecting the Kaiso binding profile in clear renal cancer cells.Epigenetics & chromatin · 2024Article
- Article
- Updated understanding of the protein-DNA recognition code used by C2H2 zinc finger proteins.Current opinion in structural biology · 2024Review
- Transposable elements as tissue-specific enhancers in cancers of endodermal lineage.Nature communications · 2023Article
- Methylation across the central dogma in health and diseases: new therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- The remodeling of Z-DNA in the mammalian germ line.Biochemical Society transactions · 2022Article
- The Essential Role of Prolines and Their Conformation in Allosteric Regulation of Kaiso Zinc Finger DNA-Binding Activity by the Adjacent C-Terminal Loop.International journal of molecular sciences · 2022Article
- Analysis of Il36a induction by C/EBPβ via a half-CRE•C/EBP element in murine macrophages in dependence of its CpG methylation level.Genes and immunity · 2021Article
- Molecular mechanism of methyl-dependent and spatial-specific DNA recognition of c-Jun homodimer.Journal of molecular modeling · 2021Article
- Relationship between High Expression of Kaiso Protein and Poor Prognosis of Lung Cancer and the Regulation Mechanism of Malignant Phenotype of Lung Cancer Cells.Journal of oncology · 2021Article
- Pinacolone-Alcohol Gas-Phase Solvation Balances as Experimental Dispersion Benchmarks.Molecules (Basel, Switzerland) · 2020Article
- A Conformational Switch in the Zinc Finger Protein Kaiso Mediates Differential Readout of Specific and Methylated DNA Sequences.Biochemistry · 2020Article
- Structural basis of specific DNA binding by the transcription factor ZBTB24.Nucleic acids research · 2019Article
- Structural insights into methylated DNA recognition by the C-terminal zinc fingers of the DNA reader protein ZBTB38.The Journal of biological chemistry · 2018Article
- Zinc Finger Readers of Methylated DNA.Molecules (Basel, Switzerland) · 2018Review
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Many eukaryotic transcription factors recognize the epigenetic marker 5-methylcytosine (mC) at CpG sites in DNA. Despite their structural diversity, methyl-CpG-binding proteins (MBPs) share a common mode of recognition of mC methyl groups that involves hydrophobic pockets and weak hydrogen bonds of the CH···O type. The zinc finger protein Kaiso possesses a remarkably high specificity for methylated over unmethylated CpG sites. A key contribution to this specificity is provided by glutamate 535 (E535), which is optimally positioned to form multiple interactions with mCpG, including direct CH···O hydrogen bonds. To examine the role of E535 and CH···O hydrogen bonding in the preferential recognition of mCpG sites, we determined the structures of wild type Kaiso (WT) and E535 mutants and characterized their interactions with methylated DNA by nuclear magnetic resonance spectroscopy (NMR), X-ray crystallography, and in vitro protein-DNA binding assays. Our data show that Kaiso favors an mCpG over a CpG site by 2 orders of magnitude in affinity and that an important component of this effect is the presence of hydrophobic and CH···O contacts involving E535. Moreover, we present the first direct evidence for formation of a CH···O hydrogen bond between an MBP and 5-methylcytosine by using experimental (NMR) and quantum mechanical chemical shift analysis of the mC methyl protons. Together, our findings uncover a critical function of methyl-specific interactions, including CH···O hydrogen bonds, that optimize the specificity and affinity of MBPs for methylated DNA and contribute to the precise control of gene expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.