The β-Globin LCR Is Not Necessary for an Open Chromatin Structure or Developmentally Regulated Transcription of the Native Mouse β-Globin Locus

Abstract

The murine β-globin locus control region (LCR) was deleted from its native chromosomal location. The ∼25 kb deletion eliminates all sequences and structures homologous to those defined as the human LCR. In differentiated ES cells and erythroleukemia cells containing the LCR-deleted chromosome, DNaseI sensitivity of the β-globin domain is established and maintained, developmental regulation of the locus is intact, and β-like globin RNA levels are reduced 5%–25% of normal. Thus, in the native murine β-globin locus, the LCR is necessary for normal levels of transcription, but other elements are sufficient to establish the open chromatin structure, transcription, and developmental specificity of the locus. These findings suggest a contributory rather than dominant function for the LCR in its native location.