Roles for histone H3K4 methyltransferase activities during immunoglobulin class-switch recombination.

Germ-line transcription of an antigen receptor gene segment is an essential feature of the targeting mechanism for DNA double-strand break formation during physiological DNA rearrangements in lymphocytes. Alterations in chromatin structure have long been postulated to regulate accessibility of recombinase activities for lymphocytes to generate antibody diversity; however, whether or not germ-line transcripts are the cause or the effect of chromatin changes at antigen receptor loci is still not clear. Methylation of histone H3 at lysine 4 is one of the most well-studied histone post-translational modifications yet we have only recently begun to understand the significance of the MLL-like H3K4 methyltransferase activities in lymphocyte function. While it is clear during lymphocyte development that H3K4me3 plays a critical role in targeting and stimulating RAG1/2 recombinase activity for V(D)J recombination, recent work suggests roles for this histone mark and different MLL-like complexes in mature B cells during immunoglobulin class-switch recombination. In this review, we focus our discussion to advances on how MLL-like complexes and H3K4 methylation may function during the germ-line transcription and recombinase targeting steps of class-switch recombination. This article is part of a Special Issue entitled: Chromatin in time and space. Published by Elsevier B.V.