ArticleProceedings of the National Academy of Sciences of the United States of America2017
H3K4me3 induces allosteric conformational changes in the DNA-binding and catalytic regions of the V(D)J recombinase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Insights into RAG Evolution from the Identification of "Missing Link" Family A RAGL Transposons.Molecular biology and evolution · 2023Article
- The chromatin determinants and Ph1 gene effect at wheat sites with contrasting recombination frequency.Journal of advanced research · 2023Article
- 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
- Phf5a regulates DNA repair in class switch recombination via p400 and histone H2A variant deposition.The EMBO journal · 2021Article
- Binding and allosteric transmission of histone H3 Lys-4 trimethylation to the recombinase RAG-1 are separable functions of the RAG-2 plant homeodomain finger.The Journal of biological chemistry · 2020Article
- V(D)J recombination, somatic hypermutation and class switch recombination of immunoglobulins: mechanism and regulation.Immunology · 2020Review
- Loss of H3K36 Methyltransferase SETD2 Impairs V(D)J Recombination during Lymphoid Development.iScience · 2020Article
- Alterations in chromatin at antigen receptor loci define lineage progression during B lymphopoiesis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The role of noncoding mutations in blood cancers.Disease models & mechanisms · 2019Review
- The histone methyltransferase Setd2 is indispensable for V(D)J recombination.Nature communications · 2019Article
- Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling.Nature communications · 2019Article
- The ESC: The Dangerous By-Product of V(D)J Recombination.Frontiers in immunology · 2019Review
- The RAG-2 Inhibitory Domain Gates Accessibility of the V(D)J Recombinase to Chromatin.Molecular and cellular biology · 2018Article
- 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
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Authors and funding
4 authors.
Funding
Abstract
V(D)J recombination is initiated by the recombination-activating gene (RAG) recombinase, consisting of RAG-1 and RAG-2 subunits. The susceptibility of gene segments to cleavage by RAG is associated with histone modifications characteristic of active chromatin, including trimethylation of histone H3 at lysine 4 (H3K4me3). Binding of H3K4me3 by a plant homeodomain (PHD) in RAG-2 stimulates substrate binding and catalysis, which are functions of RAG-1. This has suggested an allosteric mechanism in which information regarding occupancy of the RAG-2 PHD is transmitted to RAG-1. To determine whether the conformational distribution of RAG is altered by H3K4me3, we mapped changes in solvent accessibility of cysteine thiols by differential isotopic chemical footprinting. Binding of H3K4me3 to the RAG-2 PHD induces conformational changes in RAG-1 within a DNA-binding domain and in the ZnH2 domain, which acts as a scaffold for the catalytic center. Thus, engagement of H3K4me3 by the RAG-2 PHD is associated with dynamic conformational changes in RAG-1, consistent with allosteric control by active chromatin.
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