Human CD2 locus control region (LCR) sequences are shown here to be es
sential for establishing an open chromatin configuration. Transgenic m
ice carrying an hCD2 minigene attached only to the 3' CD2 transcriptio
nal enhancer exhibited variegated expression when the transgene integr
ated in the centromere. In contrast, mice carrying a transgene with ad
ditional 3' sequences showed no variegation even when the latter integ
rated in centromeric positions. This result suggests that LCRs operate
by ensuring an open chromatin configuration and that a short region,
with no enhancer activity, functions in the establishment, maintenance
, or both of an open chromatin domain.