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Transcriptional Regulation of vav, a Gene Expressed
Throughout the Hematopoietic Compartment
Sarah Ogilvy,
Andrew G. Elefanty,
Jane Visvader,
Mary L. Bath,
Alan W. Harris, and
Jerry M. Adams
From The Walter and Eliza Hall Institute of Medical Research,
Melbourne, Victoria, Australia.
The vav gene is expressed in all hematopoietic but few other
cell types. To explore its unusual compartment-wide regulation, we
cloned the murine gene, sequenced its promoter region, identified DNase
I hypersensitive (HS) sites in the chromatin, and tested their promoter
activity with a -galactosidase ( -gal) reporter gene in
cell lines and transgenic mice. Whereas fibroblasts had no HS sites, a
myeloid and an erythroid cell line contained five, located 0.2 kb
(HS1), 1.9 kb (HS2), and 3.6 kb (HS3) upstream from the transcription
start and 0.6 kb (HS4) and 10 kb (HS5) downstream. A vav DNA
fragment including HS1 promoted -gal expression in a myeloid but not
a fibroblast line. Expression in leukocytes of transgenic mice also
required HS2 and HS5. Only hematopoietic organs contained -gal, but
virtually all -gal+ cells were B or T
lymphocytes. Expression was always variegated (mosaic), and the
proportion of -gal+ cells declined with lymphoid
maturation and animal age. Thus, these vav regulatory elements
promoted hematopoietic-specific expression in vivo, at least in
lymphocytes, but the transgene was sporadically silenced. Maintaining
pan-hematopoietic expression may require additional vav
elements or an alternative reporter.
Blood, Vol. 91 No. 2 (January 15), 1998:
pp. 419-430
© 1998 by The American Society of Hematology.

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