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

We have generated mice with a targeted deletion of the P-globin locus control region (LCR). Mice homozygous for the deletion die early in embryogenesis 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 expression of all mouse P-like globin genes, but no alteration in the developmental specificity of expression. Furthermore, a DNase I-sensitive "open" chromatin conformation of the locus is established and maintained. Thus, the dominant role of the LCR in the native locus is to confer high-level transcription, and elements elsewhere in the locus are sufficient to establish and maintain an open conformation and to confer developmentally regulated globin gene expression.