Adjacent DNA elements dominantly restrict the ubiquitous activity of a novel chromatin-opening region to specific tissues

Locus control regions (LCRs) are thought to provide a dominant tissue‐specific open chromatin domain that allows for proper gene regulation by enhancers/silencers and their associated transcription factors. Expression of the T‐cell receptor alpha (TCRα) gene is limited to T cells and its locus exists in different chromatin configurations in expressing and non‐expressing cell types. Here we show that eight DNase I‐hypersensitive sites in the TCRα locus comprise an LCR that confers T‐cell compartment‐specific expression upon a linked heterologous transgene. Removal of the three 5′‐most hypersensitive sites of this LCR, containing TCRα enhancers/silencers, abolishes tissue‐differential chromatin structure and results in transgene expression in all tissues examined. The remaining five DNase I‐hypersensitive sites therefore constitute a novel control element possessing a widely active chromatin‐opening function that allows for ubiquitous expression of a linked transgene in all transgenic founder mice. Furthermore, these data show that cis ‐acting elements without inherent LCR activity can dominantly modulate chromatin structure to determine tissue‐specific gene expression in vivo .