ETS Protein–Dependent Accessibility Changes at the Immunoglobulin μ Heavy Chain Enhancer

AbstractDirected accessibility mediated by antigen-receptor gene enhancers ensures developmental stage–specific activation of V(D)J recombination. Here, we used a combination of in vitro and in vivo assays to explore the mechanisms that regulate immunoglobulin μ heavy chain gene enhancer–dependent chromatin accessibility. Ets-1 or PU.1 bound to μ enhancer–containing plasmids assembled into chromatin in vitro and increased restriction enzyme access to a proximal site. In complementary analyses, expression of PU.1 in Ets-1-containing 2017 pro-T cells or NIH 3T3 cells induced sterile Iμ transcripts at the IgH locus and increased accessibility of the endogenous μ enhancer to restriction endonucleases. These observations suggest that one role of PU.1 is to increase accessibility of the μ locus to initiate heavy chain gene expression