title: A Gata2 intronic enhancer confers its pan-endothelia-specific regulation.
abstract: 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.
authors: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
authors: Melin
authors: M
authors: Khandekar
authors: William
authors: W
authors: Brandt
authors: Yinghui
authors: Y
authors: Zhou
authors: Susan
authors: S
authors: Dagenais
authors: Thomas W
authors: TW
authors: Glover
authors: Norio
authors: N
authors: Suzuki
authors: Ritsuko
authors: R
authors: Shimizu
authors: Masayuki
authors: M
authors: Yamamoto
authors: Kim-Chew
authors: KC
authors: Lim
authors: James Douglas
authors: JD
authors: Engel
mesh_terms: 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
chemical_list: D050989:GATA2 Transcription Factor; C494712:Gata2 protein, mouse