Histone 3 lysine 4 methylation during the pre-B to immature B-cell transition

Abstract

The relationship between chromatin modification and lymphocyte development is still poorly understood. Here we show a correlation between methylation of lysine 4 on histone 3 (H3-K4) and activation of several loci required for the pre-B cell to immature B-cell developmental transition. A critical step in this transition is the induction of V(D)J recombination at the Igκ locus. Upon activation of Igκ recombination, a >10-fold enrichment of both di-and trimethylated H3-K4 is observed at Jκ targeting signals, but not at an analogous targeting signal in the T-cell receptor a locus or, surprisingly, at several Vκ signals. However, H3-K4 methylation is restricted to the actively recombining fraction of Jκ recombination targeting signals, consistent with a direct relationship between H3-K4 methylation and signal activity. Correlations between increased H3-K4 methylation and induction of transcription are also observed at some, but not all, loci where transcription is induced. H3-K4 methylation may therefore be a widely used but not universal means for controlling chromatin activity in this developmental transition. © Oxford University Press 2004; all rights reserved.