ArticleNucleic acids research2016
RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2.
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 20 papers.
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Who cites it
20 citing papers in PubMed.
- Proximity-based proteomic profiling uncovers distinct interactome of human RAG1 and RAG2.Acta biochimica et biophysica Sinica · 2026Article
- Physiological upregulation of RAG1 expression compromises the survival of CD4Frontiers in immunology · 2026Article
- The nonamer code for RAG-mediated recombination in vivo.Nucleic acids research · 2025Article
- Zinc and its binding proteins: essential roles and therapeutic potential.Archives of toxicology · 2025Review
- Insights into RAG Evolution from the Identification of "Missing Link" Family A RAGL Transposons.Molecular biology and evolution · 2023Article
- The recombinase activating genes: architects of immune diversity during lymphocyte development.Frontiers in immunology · 2023Review
- The 3D enhancer network of the developing T cell genome is shaped by SATB1.Nature communications · 2022Article
- An updated definition of V(D)J recombination signal sequences revealed by high-throughput recombination assays.Nucleic acids research · 2022Article
- Structural insights into the evolution of the RAG recombinase.Nature reviews. Immunology · 2022Review
- V(D)J Recombination: Recent Insights in Formation of the Recombinase Complex and Recruitment of DNA Repair Machinery.Frontiers in cell and developmental biology · 2022Review
- The RAG1 N-terminal region regulates the efficiency and pathways of synapsis for V(D)J recombination.The Journal of experimental medicine · 2021Article
- RAG enhances BCR-ABL1-positive leukemic cell growth through its endonuclease activity in vitro and in vivo.Cancer science · 2021Article
- Review
- Nucleolar localization of RAG1 modulates V(D)J recombination activity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The ESC: The Dangerous By-Product of V(D)J Recombination.Frontiers in immunology · 2019Review
- A Lamina-Associated Domain Border Governs Nuclear Lamina Interactions, Transcription, and Recombination of the Tcrb Locus.Cell reports · 2018Article
- Epigenetic modifications of the VImmunology · 2017Article
- New insights into the evolutionary origins of the recombination-activating gene proteins and V(D)J recombination.The FEBS journal · 2017Review
- Local Chromatin Features Including PU.1 and IKAROS Binding and H3K4 Methylation Shape the Repertoire of Immunoglobulin Kappa Genes Chosen for V(D)J Recombination.Frontiers in immunology · 2017Article
- Genetics and Molecular Biology of Epstein-Barr Virus-Encoded BART MicroRNA: A Paradigm for Viral Modulation of Host Immune Response Genes and Genome Stability.Journal of immunology research · 2017Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The RAG1/RAG2 endonuclease initiates V(D)J recombination at antigen receptor loci but also binds to thousands of places outside of these loci. RAG2 localizes directly to lysine 4 trimethylated histone 3 (H3K4me3) through a plant homeodomain (PHD) finger. The relative contribution of RAG2-dependent and RAG1-intrinsic mechanisms in determining RAG1 binding patterns is not known. Through analysis of deep RAG1 ChIP-seq data, we provide a quantitative description of the forces underlying genome-wide targeting of RAG1. Surprisingly, sequence-specific DNA binding contributes minimally to RAG1 targeting outside of antigen receptor loci. Instead, RAG1 binding is driven by two distinct modes of interaction with chromatin: the first is driven by H3K4me3, promoter-focused and dependent on the RAG2 PHD, and the second is defined by H3K27Ac, enhancer-focused and dependent on 'non-core' portions of RAG1. Based on this and additional chromatin and genomic features, we formulated a predictive model of RAG1 targeting to the genome. RAG1 binding sites predicted by our model correlate well with observed patterns of RAG1-mediated breaks in human pro-B acute lymphoblastic leukemia. Overall, this study provides an integrative model for RAG1 genome-wide binding and off-target activity and reveals a novel role for the RAG1 non-core region in RAG1 targeting.
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