The mouse 0-globin locus control region: hypersensitive

The human /3-globin LCR plays a key role in the transcriptional regulation of the /3-globin locus and comprises four erythroid specific ONase I hypersensitive sites, designated 5'HS1- 4. We have now isolated genomic clones containing 5'HS3 and 5'HS4 of the mouse /3-globin LCR. 5'HS3 and 5'HS4 are located 15 kb and 22 kb upstream of the mouse ey-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 /3-globin LCRs. Finally, the cloning of mouse 5'HS3 and 5'HS4 will facilitate the molecular analysis of LCR function in the mouse model