IMMUNOGLOBULIN HEAVY-CHAIN AND CD3 DELTA-CHAIN GENE ENHANCERS ARE DNASE I-HYPERSENSITIVE IN HEMATOPOIETIC PROGENITOR CELLS

Multipotential interleukin 3-dependent non-immortalized murine hemopoietic progenitor cells have DNase 1-hypersensitive sites in the immunoglobulin heavy-chain and CD3-delta enhancers and transcribe germ-line T-cell antigen receptor gamma-chain (TCR-gamma), but not IgM or TCR-beta, genes. Induction of myeloid differentiation in these cells closes down expression and/or transcriptional accessibility of the immunoglobulin heavy-chain and TCR-gamma genes. The CD3-delta enhancer region remains DNase I-hypersensitive but closes down in B cells. In embryonic stem cells and pan-mesodermal cells, these genes or enhancer regions are neither expressed nor DNase I-hypersensitive. These data suggest that lineage potential may be programmed, at least in part, by alterations in the accessibility or conformation of regulatory regions of genes and that some promiscuity of gene expression and/or accessibility can precede lineage commitment and maturation in progenitor cells induced to self-renew by interleukin 3.