Vezf1: A transcriptional regulator of the endothelium
Heart Defects, Congenital
© Cambridge University Press 2007 and 2009.This chapter summarizes our current knowledge of vascular endothelial zinc finger 1 (Vezf1) and its human orthologue DB1 and their role in vascular biology. We describe the unique features of the Vezf1 gene and its homologues, and we will present evidence that Vezf1 acts as a transcription factor. Finally, we discuss possible roles that Vezf1 plays in the endothelium during development and in angiogenesis. Mouse Vezf1 originally was identified using a retroviral “gene trap” screen for early cardiovascular genes in mouse embryonic stem (ES) cells and embryos (1–4). During embryogenesis, Vezf1 expression is localized in vascular endothelium (4), as well as neuronal and mesodermal tissues. Under in vitro conditions, Vezf1 expression has been reported in cultured endothelial cells (ECs) such as human umbilical vein ECs (HUVECs), mouse EOMA and yolk sac–derived ECs, hematopoietic cell lines (T, pre-B, erythroleukemia cells, macrophages) (4), and a fetal liver–derived stromal cell line (5). The human orthologue, DB1 (also termed ZF161), was first isolated from Jurkat T cells as a protein that binds to a GT/GC-rich region in the human interleukin (IL)-3 promoter (6). In addition, DB1 was found to be up regulated during differentiation of dendritic cells from monocytes by cDNA microarray analysis (7). VEZF1 IS HIGHLY CONSERVED AMONG VERTEBRATES One of the striking features of Vezf1 is the high extent of conservation of the gene structure and the nucleotide and amino acid sequences (4; F. Kuhnert and H. Stuhlmann, unpublished observations). The murine Vezf1 gene contains six exons and five introns and spans a total length of 16.3-kb on chromosome 11.
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