Abstract
V(D)J recombination is the process by which the diversity of antigen receptor genes is generated and is also indispensable for lymphocyte development. This recombination event occurs in a cell lineage- and stage-specific manner, and is carefully controlled by chromatin structure and ordered histone modifications. The recombinationally active V(D)J loci areassociated with hypermethylation at lysine4 of histone H3 and hyperacetylation of histones H3/H4. The recombination activating gene 1 (RAG1) and RAG2 complex initiates recombination by introducing double-strand DNA breaks at recombination signal sequences (RSS) adjacent to each coding sequence. To be recognized by the RAG complex, RSS sites must bewithin an open chromatin context. In addition, the RAG complex specifically recognizes hypermethylated H3K4 through its plant homeodomain (PHD) finger in the RAG2 C terminus, whichstimulates RAGcatalytic activity via that interaction. In this review, we describe how histone methylation controls V(D)J recombination and discuss its potential role in lymphoid malignancy by mistargeting the RAG complex.
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