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.
Laboratory of Genome Integrity, National Cancer Institue, National Institutes of Health, Bethesda, MD, USA. jeremy.daniel@cpr.ku.dk
Jeremy A
JA
Daniel
André
A
Nussenzweig
D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D017578:Immunoglobulin Class Switching; D011499:Protein Processing, Post-Translational; D011946:Receptors, Antigen / Q000235:genetics; D060152:V(D)J Recombination
D002843:Chromatin; D006657:Histones; D011946:Receptors, Antigen; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase