The mouse beta-globin locus control region: hypersensitive sites 3 and 4.

The human beta-globin LCR plays a key role in the transcriptional regulation of the beta-globin locus and comprises four erythroid specific DNase I hypersensitive sites, designated 5'HS1-4. We have now isolated genomic clones containing 5'HS3 and 5'HS4 of the mouse beta-globin LCR. 5'HS3 and 5'HS4 are located 15 kb and 22 kb upstream of the mouse epsilon y-globin gene, respectively. Sequence analysis of murine 5'HS3 and 5'HS4 reveals a significant degree of sequence conservation with their human homologues, including the presence of recognition sites for functionally relevant transcription factors. 5'HS3 and 5'HS4 regions were found to form hypersensitive sites in nuclei from murine erythroid cells, but not in nuclei from a variety of nonerythroid haematopoietic cell lines. Analysis of different mouse strains revealed the existence of a polymorphism that alters the spacing between 5'HS3 and 5'HS4. Taken together, our results emphasize the extent of evolutionary conservation and complexity of mammalian beta-globin LCRs. Finally, the cloning of mouse 5'HS3 and 5'HS4 will facilitate the molecular analysis of LCR function in the mouse model.