ArticleNucleic acids research2016
Distinctive Klf4 mutants determine preference for DNA methylation status.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed, 28 citations in OpenAlex.
- Whole-genome 5-hydroxymethylation profiling of human neurons for regulatory and biological insight.Epigenetics & chromatin · 2026Article
- Zinc-finger transcription factor Fzf1 binds to its target DNA in a non-canonical manner.Nucleic acids research · 2026Article
- KDM1A-driven RNF81 downregulation promotes gastric cancer progression via KLF4 destabilization.Oncogene · 2025Article
- DNA-binding proteins from MBD through ZF to BEN: recognition of cytosine methylation status by one arginine with two conformations.Nucleic acids research · 2024Article
- Structural analysis of the BisI family of modification dependent restriction endonucleases.Nucleic acids research · 2024Article
- Mutations in linker-2 of KLF1 impair expression of membrane transporters and cytoskeletal proteins causing hemolysis.Nature communications · 2024Article
- EKLF/Klf1 regulates erythroid transcription by its pioneering activity and selective control of RNA Pol II pause-release.Cell reports · 2022Article
- Structurally-discovered KLF4 variants accelerate and stabilize reprogramming to pluripotency.iScience · 2022Article
- Proteins That Read DNA Methylation.Advances in experimental medicine and biology · 2022Article
- An Overview of Epigenetic Methylation in Pancreatic Cancer Progression.Frontiers in oncology · 2022Review
- Structural basis for human ZBTB7A action at the fetal globin promoter.Cell reports · 2021Article
- Liquid condensation of reprogramming factor KLF4 with DNA provides a mechanism for chromatin organization.Nature communications · 2021Article
- Large DNA Methylation Nadirs Anchor Chromatin Loops Maintaining Hematopoietic Stem Cell Identity.Molecular cell · 2020Article
- Long non-coding RNA LINC00673 silencing inhibits proliferation and drug resistance of prostate cancer cells via decreasing KLF4 promoter methylation.Journal of cellular and molecular medicine · 2020Article
- The diverse roles of DNA methylation in mammalian development and disease.Nature reviews. Molecular cell biology · 2019Review
- Corrupted DNA-binding specificity and ectopic transcription underpin dominant neomorphic mutations in KLF/SP transcription factors.BMC genomics · 2019Article
- DNA methylation in mice is influenced by genetics as well as sex and life experience.Nature communications · 2019Article
- DNA Methylation Readers and Cancer: Mechanistic and Therapeutic Applications.Frontiers in oncology · 2019Review
- Detecting and interpreting DNA methylation marks.Current opinion in structural biology · 2018Review
- Zinc Finger Readers of Methylated DNA.Molecules (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Reprogramming of mammalian genome methylation is critically important but poorly understood. Klf4, a transcription factor directing reprogramming, contains a DNA binding domain with three consecutive C2H2 zinc fingers. Klf4 recognizes CpG or TpG within a specific sequence. Mouse Klf4 DNA binding domain has roughly equal affinity for methylated CpG or TpG, and slightly lower affinity for unmodified CpG. The structural basis for this key preference is unclear, though the side chain of Glu446 is known to contact the methyl group of 5-methylcytosine (5mC) or thymine (5-methyluracil). We examined the role of Glu446 by mutagenesis. Substituting Glu446 with aspartate (E446D) resulted in preference for unmodified cytosine, due to decreased affinity for 5mC. In contrast, substituting Glu446 with proline (E446P) increased affinity for 5mC by two orders of magnitude. Structural analysis revealed hydrophobic interaction between the proline's aliphatic cyclic structure and the 5-methyl group of the pyrimidine (5mC or T). As in wild-type Klf4 (E446), the proline at position 446 does not interact directly with either the 5mC N4 nitrogen or the thymine O4 oxygen. In contrast, the unmethylated cytosine's exocyclic N4 amino group (NH
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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.