A Gata2 intronic enhancer confers its pan-endothelia-specific regulation.
GATA-2, a transcription factor that has been shown to play important roles in multiple organ systems during embryogenesis, has been ascribed the property of regulating the expression of numerous endothelium-specific genes. However, the transcriptional regulatory hierarchy governing Gata2 activation in endothelial cells has not been fully explored. Here, we document GATA-2 endothelial expression during embryogenesis by following GFP expression in Gata2-GFP knock-in embryos. Using founder transgenic analyses, we identified a Gata2 endothelium enhancer in the fourth intron and found that Gata2 regulation by this enhancer is restricted to the endocardial, lymphatic and vascular endothelium. Whereas disruption of three ETS-binding motifs within the enhancer diminished its activity, the ablation of its single E box extinguished endothelial enhancer-directed expression in transgenic mice. Development of the endothelium is known to require SCL (TAL1), and an SCL-E12 (SCL-Tcfe2a) heterodimer can bind the crucial E box in the enhancer in vitro. Thus, GATA-2 is expressed early in lymphatic, cardiac and blood vascular endothelial cells, and the pan-endothelium-specific expression of Gata2 is controlled by a discrete intronic enhancer.
Khandekar
Melin
M
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
Brandt
William
W
Zhou
Yinghui
Y
Dagenais
Susan
S
Glover
Thomas W
TW
Suzuki
Norio
N
Shimizu
Ritsuko
R
Yamamoto
Masayuki
M
Lim
Kim-Chew
KC
Engel
James Douglas
JD
D000818:Animals; D001483:Base Sequence; D018244:Chromosomes, Artificial, Yeast; D004727:Endothelium / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D050989:GATA2 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D007438:Introns; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data
D050989:GATA2 Transcription Factor; C494712:Gata2 protein, mouse