THE BETA-GLOBIN LCR IS NOT NECESSARY FOR AN OPEN CHROMATIN STRUCTURE OR DEVELOPMENTALLY-REGULATED TRANSCRIPTION OF THE NATIVE MOUSE BETA-GLOBIN LOCUS

The murine beta-globin locus control region (LCR) was deleted from its native chromosomal location. The similar to 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, DNasel sensitivity of the beta-globin doma in is established and maintained, developmental regulation of the locu s is intact, and beta-like globin RNA levels are reduced 5%-25% of nor mal. Thus, in the native murine beta-globin locus, the LCR is necessar y for normal levels of transcription, but other elements are sufficien t to establish the open chromatin structure, transcription, and develo pmental specificity of the locus. These findings suggest a contributor y rather than dominant function for the LCR in its native location.