beta-globin gene switching and DNase I sensitivity of the endogenous beta-globin locus in mice do not require the locus control region

We have generated mice with a targeted deletion of the P-globin locus contr ol region (LCR). Mice homozygous for the deletion die early in embryogenesi s but can be rescued with a YAC containing the human P-globin locus. After germline passage, deletion of the LCR leads to a severe reduction in expres sion of all mouse P-like globin genes, but no alteration in the development al specificity of expression. Furthermore, a DNase I-sensitive "open" chrom atin conformation of the locus is established and maintained. Thus, the dom inant role of the LCR in the native locus is to confer high-level transcrip tion, and elements elsewhere in the locus are sufficient to establish and m aintain an open conformation and to confer developmentally regulated globin gene expression.