angiopoietin-2 is a direct transcriptional target of tal1, lyl1 and lmo2 in endothelial cellstal1 angiopoietin-2直接转录目标,lyl1 lmo2内皮细胞.pdfVIP

Angiopoietin-2 Is a Direct Transcriptional Target of TAL1, LYL1 and LMO2 in Endothelial Cells 1,2,3. 1,2,3. 1,2,3¤a 1,2,3 ´ 1,2,3 Virginie Deleuze , Rawan El-Hajj , Elias Chalhoub , Christiane Dohet , Valerie Pinet , 4¤b ` 1,2,3 Philippe Couttet , Daniele Mathieu * ´ ´ ´ ´ ´ 1 Institut de Genetique Moleculaire de Montpellier UMR 5535 CNRS, Montpellier, France, 2 Universite Montpellier 2, Montpellier, France, 3 Universite Montpellier 1, Montpellier, France, 4 The Sanger Institute, Cambridge, United Kingdom Abstract The two related basic helix–loop-helix, TAL1 and LYL1, and their cofactor LIM-only-2 protein (LMO2) are present in blood and endothelial cells. While their crucial role in early hematopoiesis is well established, their function in endothelial cells and especially in angiogenesis is less understood. Here, we identified ANGIOPOIETIN-2 (ANG-2), which encodes a major regulator of angiogenesis, as a direct transcriptional target of TAL1, LYL1 and LMO2. Knockdown of any of the three transcription factors in human blood and lymphatic endothelial cells caused ANG-2 mRNA and protein down-regulation. Transient transfections showed that the full activity of the ANG-2 promoter required the integrity of a highly conserved Ebox-GATA composite element. Accordingly, chromatin immunoprecipitation assays demonstrated that TAL1, LYL1, LMO2 and GATA2 occupied this region of ANG-2 promoter in human endothelial c