Description and Targeted Deletion of 5 8 Hypersensitive Site 5 and 6 of the Mouse b - Globin Locus Control Region

The most upstream hypersensitive site (HS) of the b-globin locus control region (LCR) in humans (58 HS 5) and chickens (58 HS 4) can act as an insulating element in some gain of function assays and may demarcate a b-globin domain. We have mapped the most upstream HSs of the mouse b-globin LCR and sequenced this region. We find that mice have a region homologous to human 58 HS 5 that is associated with a minor HS. In addition we map a unique HS upstream of 58 HS 5 and refer to this novel site as mouse 58 HS 6. We have also generated mice containing a targeted deletion of the region containing 58 HS 5 and 6. We find that after excision of the selectable marker in vivo, deletion of 58 HS 5 and 6 has a minimal effect on transcription and does not prevent formation of the remaining LCR HSs. Taken together these findings suggest that the most upstream HSs of the mouse b-globin LCR are not necessary for maintaining the b-globin locus in an active configuration or to protect it from a surrounding repressive chromatin environment. r 1998 by The American Society of Hematology.