The basic helix-loop-helix TAL-1/SCL essential for hematopoietic development is also required during vascular development for embryonic angiogenesis. We reported that TAL-1 acts positively on postnatal angiogenesis by stimulating endothelial morphogenesis. Here, we investigated the functional consequences of TAL-1 silencing in human primary endothelial cells. We found that TAL-1 knockdown caused the inhibition of in vitro tubulomorphogenesis, which was associated with a dramatic reduction in vascular endothelial cadherin (VE-cadherin) at intercellular junctions. Consistently, silencing of TAL-1 as well as of its cofactors E47 and LMO2 down-regulated VE-cadherin at both the mRNA and the protein level. Endogenous VE-cadherin transcription could be activated in nonendothelial HEK-293 cells by the sole concomitant ectopic expression of TAL-1, E47, and LMO2. Transient transfections in human primary endothelial cells derived from umbilical vein (HUVECs) demonstrated that VE-cadherin promoter activity was dependent on the integrity of a specialized E-box associated with a GATA motif and was maximal with the coexpression of the different components of the TAL-1 complex. Finally, chromatin immunoprecipitation assays showed that TAL-1 and its cofactors occupied the VE-cadherin promoter in HUVECs. Together, these data identify VE-cadherin as a bona fide target gene of the TAL-1 complex in the endothelial lineage, providing a first clue to TAL-1 function in angiogenesis.
TAL-1/SCL and its partners E47 and LMO2 up-regulate VE-cadherin expression in endothelial cells
Deleuze, V.; Chalhoub, E.; El-Hajj, R.; Dohet, C.; Le Clech, M.; Couraud, P. O.; Huber, P.; Mathieu, D.
Mol Cell Biol
2007-04 / vol 27 / pages 2687-97
Humans; Cells, Cultured; Amino Acid Sequence; Molecular Sequence Data; Protein Binding; Promoter Regions (Genetics); Base Sequence; Basic Helix-Loop-Helix Transcription Factors/*physiology; Drug Combinations; Proto-Oncogene Proteins/*physiology; DNA-Binding Proteins/*physiology; Neovascularization, Physiologic; Collagen; Laminin; Proteoglycans; *Up-Regulation; Antigens, CD/*biosynthesis/genetics; Cadherins/*biosynthesis/genetics; Endothelial Cells/*metabolism/physiology; Endothelium, Vascular/cytology; Metalloproteins/*physiology; TCF Transcription Factors/*physiology