A Plant Homeodomain in Rag-2 that Binds Hypermethylated Lysine 4 of Histone H3 Is Necessary for Efficient Antigen-Receptor-Gene Rearrangement
| Autor: | Yun Liu, Ranjan Sen, Tirtha Chakraborty, Ramesh Subrahmanyam, Stephen Desiderio |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Immunoglobulin gene
Blotting Western Immunology Biology Polymerase Chain Reaction Histones Mice 03 medical and health sciences Histone H3 0302 clinical medicine Histone H1 Histone H2A Animals Immunoprecipitation Histone code Immunology and Allergy MOLIMMUNO 030304 developmental biology Gene Rearrangement Homeodomain Proteins B-Lymphocytes 0303 health sciences Genes Immunoglobulin Lysine Stem Cells hemic and immune systems Gene rearrangement DNA Methylation Surface Plasmon Resonance Molecular biology Chromatin DNA-Binding Proteins Receptors Antigen Infectious Diseases PHD finger Histone methyltransferase Electrophoresis Polyacrylamide Gel 030215 immunology |
| Zdroj: | Immunity. 27(4):561-571 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2007.09.005 |
| Popis: | SummaryV(D)J recombination is initiated by the recombination activating gene (RAG) proteins RAG-1 and RAG-2. The ability of antigen-receptor-gene segments to undergo V(D)J recombination is correlated with spatially- and temporally-restricted chromatin modifications. We have found that RAG-2 bound specifically to histone H3 and that this binding was absolutely dependent on dimethylation or trimethylation at lysine 4 (H3K4me2 or H3K4me3). The interaction required a noncanonical plant homeodomain (PHD) that had previously been described within the noncore region of RAG-2. Binding of the RAG-2 PHD finger to chromatin across the IgH D-JH-C locus showed a strong correlation with the distribution of trimethylated histone H3 K4. Mutation of a conserved tryptophan residue in the RAG-2 PHD finger abolished binding to H3K4me3 and greatly impaired recombination of extrachromosomal and endogenous immunoglobulin gene segments. Together, these findings are consistent with the interpretation that recognition of hypermethylated histone H3 K4 promotes efficient V(D)J recombination in vivo. |
| Databáze: | OpenAIRE |
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