Modifications to the core histones are thought to contribute to ESC pluripotency 
by priming tissue-specific promoters and enhancers for later activation. 
However, it is unclear how these marks are targeted in ESCs and maintained 
during differentiation. Here, we show that the ESC factor Sox2 targets H3K4 
methylation to monovalent and bivalent domains. In ESCs, Sox2 contributes to the 
formation of a monovalent mark at an enhancer in the pro/pre-B cell-specific 
lambda5-VpreB1 locus. Binding of Foxd3 suppresses intergenic transcription of 
the enhancer and surrounding sequences. In pro-B cells, enhancer activity is 
dependent on the Sox and Fox binding sites, and the enhancer is bound by Sox4, 
which is required for efficient expression of lambda5. Our results lead us to 
propose a factor relay model whereby ESC factors establish active epigenetic 
marks at tissue specific elements before being replaced by cell type-specific 
factors as cells differentiate.