A Plant Homeodomain in Rag-2 that Binds Hypermethylated Lysine 4 of Histone H3 Is Necessary for Efficient Antigen-Receptor-Gene Rearrangement

Yun Liu, Ramesh Subrahmanyam, Tirtha Chakraborty, Ranjan Sen, Stephen Desiderio

Research output: Contribution to journalArticlepeer-review

Abstract

V(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.

Original languageEnglish (US)
Pages (from-to)561-571
Number of pages11
JournalImmunity
Volume27
Issue number4
DOIs
StatePublished - Oct 26 2007

Keywords

  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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