ArticleNature2007
RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination.
Article in Nature, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 279 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
279 citing papers in PubMed, 1 synthesis or guideline pooled it, 460 citations in OpenAlex.
- Prognostic significance of ING3 expression in patients with cancer: A systematic review and meta-analysis.Frontiers in oncology · 2023Pooled it
- Epigenetic regulation of B cell tolerance and dysfunction in autoimmune disease.Nature reviews. Immunology · 2026Review
- A Synthetic Platform for Antibody Junctional Diversification Beyond Natural Constraints.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A revised model for PHF20L1 Tudor function: DNA binding overrides methylation selectivity on nucleosomes.The Journal of biological chemistry · 2026Article
- The Semantics and Mechanisms of Enhancers and Promoters: "What Is True forAnnual review of biochemistry · 2026Review
- CFP1-mediated H3K4me3 broad domains control early B cell lineage fate determination.Nucleic acids research · 2026Article
- Proximity-based proteomic profiling uncovers distinct interactome of human RAG1 and RAG2.Acta biochimica et biophysica Sinica · 2026Article
- Clinical immunology in chromatinopathies: a scoping review.Frontiers in immunology · 2026Article
- Physiological upregulation of RAG1 expression compromises the survival of CD4Frontiers in immunology · 2026Article
- Jk Dna Gaga Motifs Are Required for Local Nucleosome Remodeling and Vk-jk Recombination.Research square · 2025Article
- The nonamer code for RAG-mediated recombination in vivo.Nucleic acids research · 2025Article
- Calibrated Variant Effect Prediction at the Residue Level Using Conditional Score Distributions.bioRxiv : the preprint server for biology · 2025Article
- Nucleosome context regulates chromatin reader preference.Nucleic acids research · 2025Article
- Role of Histone H3 Lysine 4 Methylation in Chromatin Biology.Molecules (Basel, Switzerland) · 2025Review
- How RAG1/2 evolved from ancestral transposases to initiate V(D)J recombination without transposition.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Building a neural network model to define DNA sequence specificity in V(D)J recombination.Nucleic acids research · 2025Article
- The insulator EACBE regulates V(D)J recombination of Tcrd gene by modulating chromatin organization.Frontiers in immunology · 2025Article
- Article
- Non-canonical functions of enhancers: regulation of RNA polymerase III transcription, DNA replication, and V(D)J recombination.Trends in genetics : TIG · 2024Article
- Interrogating epigenetic mechanisms with chemically customized chromatin.Nature reviews. Genetics · 2024Review
219 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
Nuclear processes such as transcription, DNA replication and recombination are dynamically regulated by chromatin structure. Eukaryotic transcription is known to be regulated by chromatin-associated proteins containing conserved protein domains that specifically recognize distinct covalent post-translational modifications on histones. However, it has been unclear whether similar mechanisms are involved in mammalian DNA recombination. Here we show that RAG2--an essential component of the RAG1/2 V(D)J recombinase, which mediates antigen-receptor gene assembly--contains a plant homeodomain (PHD) finger that specifically recognizes histone H3 trimethylated at lysine 4 (H3K4me3). The high-resolution crystal structure of the mouse RAG2 PHD finger bound to H3K4me3 reveals the molecular basis of H3K4me3-recognition by RAG2. Mutations that abrogate RAG2's recognition of H3K4me3 severely impair V(D)J recombination in vivo. Reducing the level of H3K4me3 similarly leads to a decrease in V(D)J recombination in vivo. Notably, a conserved tryptophan residue (W453) that constitutes a key structural component of the K4me3-binding surface and is essential for RAG2's recognition of H3K4me3 is mutated in patients with immunodeficiency syndromes. Together, our results identify a new function for histone methylation in mammalian DNA recombination. Furthermore, our results provide the first evidence indicating that disrupting the read-out of histone modifications can cause an inherited human disease.
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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.