Transcriptional regulators act in concert to specify distinct developmental stages, but how such networks are established during development remains unclear. In Immunity, Mercer et al. describe the evolving enhancer repertoire during B cell differentiation by long-term culture of hematopoietic stem cells generated by enforcement of expression of the E-protein inhibitor Id2. Induced downregulation of Id2 allows differentiation. The presence of monomethylation of histone H3 at Lys4 demonstrates that lineage-restricted enhancers are already primed in multipotent progenitors. The enhancers of genes with similar activity are enriched for distinct cis-regulatory codes. For example, genes upregulated during B cell development frequently contain binding sites for the transcription factors PU.1 and Runx at the hematopoietic stem cell stage and for the transcription factors E2A and, ultimately, EBF at the commitment stage, whereas genes repressed in B cells contained binding sites for transcription factors E2A and Fli in islands of monomethylated histone H3 Lys4 in committed B cells.

Immunity (15 September 2011) doi:10.1016/j.immuni.2011.06.013