TAL-1/SCL and its partners E47 and LMO2 up-regulate VE-cadherin expression in endothelial cells.
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.
Deleuze
Virginie
V
Institut de Génétique Moléculaire de Montpellier CNRS, UMR5535, Montpellier, France.
Chalhoub
Elias
E
El-Hajj
Rawan
R
Dohet
Christiane
C
Le Clech
Mikaël
M
Couraud
Pierre-Olivier
PO
Huber
Philippe
P
Mathieu
Danièle
D
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D003094:Collagen; D004268:DNA-Binding Proteins / Q000502:physiology*; D004338:Drug Combinations; D042783:Endothelial Cells / Q000378:metabolism* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D060588:LIM Domain Proteins; D007797:Laminin; D008667:Metalloproteins / Q000502:physiology*; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D051820:TCF Transcription Factors / Q000502:physiology*; D058125:Transcription Factor 7-Like 1 Protein; D015854:Up-Regulation; D000099152:Cadherin 5
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D003094:Collagen; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D060588:LIM Domain Proteins; D007797:Laminin; D008667:Metalloproteins; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D000099152:Cadherin 5; C085117:LMO2 protein, human; C544912:TCF7L1 protein, human; C059485:matrigel; C067143:TAL1 protein, human