DESCRIPTION AND TARGETED DELETION OF 5' HYPERSENSITIVE SITE-5 AND SITE-6 OF THE MOUSE BETA-GLOBIN LOCUS-CONTROL REGION

The most upstream hypersensitive site (HS) of the beta-globin locus co ntrol region (LCR) in humans (5' HS 5) and chickens (5' HS 4) can act as an insulating element in some gain of function assays and may demar cate a beta-globin domain. We have mapped the most upstream HSs of the mouse beta-globin LCR and sequenced this region. We find that mice ha ve a region homologous to human 5' HS 5 that is associated with a mino r HS, In addition we map a unique HS upstream of 5' HS 5 and refer to this novel site as mouse 5' HS 6. We have also generated mice containi ng a targeted deletion of the region containing 5' HS 5 and 6, We find that after excision of the selectable marker in vivo, deletion of 5' HS 5 and 6 has a minimal effect on transcription and does not prevent formation of the remaining LCR HSs. Taken together these findings sugg est that the most upstream HSs of the mouse beta-globin LCR are not ne cessary for maintaining the beta-globin locus in an active configurati on or to protect it from a surrounding repressive chromatin environmen t. (C) 1998 by The American Society of Hematology.