The GATA family of transcription factors are zinc finger proteins that bind directly to the consensus motif (T/A) GATA (A/G). GATA factors are highly conserved throughout evolution. The mammalian family consists of six GATA-1 to -6. The proteins have been classified into two subgroups, according to sequence homology and expression patterns: (a) GATA-1, -2, and -3, which are expressed predominantly in hematopoietic cells; and (b) GATA-4, -5, and -6, which are primarily expressed in heart, gastrointestinal tract, and embryonic endoderm (1,2). Endothelial cells (ECs) have been shown to express GATA-2, -3, and -6. With the exception of GATA- 5, disruption of GATA factors in mice results in embryonic lethality. This chapter reviews the role for these proteins in EC biology (summarized in Table 88–1).

GATA-2

GATA-2 is widely considered to be a critical mediator of hematopoietic cells. Although it is expressed in ECs, its role in this cell type is less well defined. Several in vitro studies have demonstrated a role for GATA-2 in mediating basal gene expression in ECs. In the early 1990s, two groups independently cloned human GATA-2 and reported that GATA-2 transactivates the pre-proendothelin-1 promoter in bovine aortic ECs (3,4). Additional studies have implicated GATA-2 in the basal regulation of von Willebrand factor (vWF) (5), utrophin B (6), platelet-endothelial cell adhesion molecule (PECAM)- 1 (7,8), Tie2 (9), and endothelial nitric oxide synthase (eNOS) (10).

In addition to controlling basal expression of EC-specific genes,GATA-2also serves asanimmediate early gene, coupling changes in the extracellular environment to an alteration inEC phenotype.