N. Minegishi et al., The mouse GATA-2 gene is expressed in the para-aortic splanchnopleura and aorta-gonads and mesonephros region, BLOOD, 93(12), 1999, pp. 4196-4207
We previously reported that the mouse GATA-2 gene is regulated by two alter
native promoters (Minegishi et al, J Biol Chem, 273:3625, 1998). Although t
he more proximal IG (general) promoter is active in almost all GATA-2-expre
ssing cells, the distal IS (specific) promoter activity was selectively det
ected in hematopoietic tissues but not in other mesodermal tissues. We repo
rt here in vivo analysis of the GATA-2 locus and its regulatory characteris
tics in hematopoietic tissues of transgenic mice. Transgenes containing 6 o
r 7 kbp of sequence flanking the 5' end of the IS first exon direct express
ion of beta-galactosidase or green fluorescent protein (GFP) reporter genes
specifically to the para-aortic splanchnopleura, aorta-gonads, and mesonep
hros (AGM) region, and in the neural tissues. In situ hybridization analysi
s showed that reporter gene expression specifically recapitulates the endog
enous expression profile of GATA-2 in these tissues. The flk-1, CD34, c-kit
, and CD45 antigens were identified in the GFP-positive cells from the AGM
region and fetal liver, indicating that GATA-2 is expressed in immature hem
atopoietic cells. Deletion of 3.5 kbp from the 5' end of the 6.0 kbp IS pro
moter construct, including one of the DNase I hypersensitive sites, complet
ely abolished hematopoietic expression. These experiments describe an early
developmental GATA-2 hematopoietic enhancer located between 6.0 and 2.5 kb
p 5' to the IS exon. (C) 1999 by The American Society of Hematology.