title: Feedback Mechanisms Regulate Ets Variant 2 (Etv2) Gene Expression and Hematoendothelial Lineages.
abstract: Etv2 is an essential transcriptional regulator of hematoendothelial lineages during embryogenesis. Although Etv2 downstream targets have been identified, little is known regarding the upstream transcriptional regulation of Etv2 gene expression. In this study, we established a novel methodology that utilizes the differentiating ES cell and embryoid body system to define the modules and enhancers embedded within the Etv2 promoter. Using this system, we defined an autoactivating role for Etv2 that is mediated by two adjacent Ets motifs in the proximal promoter. In addition, we defined the role of VEGF/Flk1-Calcineurin-NFAT signaling cascade in the transcriptional regulation of Etv2. Furthermore, we defined an Etv2-Flt1-Flk1 cascade that serves as a negative feedback mechanism to regulate Etv2 gene expression. To complement and extend these studies, we demonstrated that the Flt1 null embryonic phenotype was partially rescued in the Etv2 conditional knockout background. In summary, these studies define upstream and downstream networks that serve as a transcriptional rheostat to regulate Etv2 gene expression.
authors.affiliation: Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, Minnesota 55455.
authors.forename: Naoko
authors.initials: N
authors.lastname: Koyano-Nakagawa
authors.affiliation: Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, Minnesota 55455.
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Shi
authors.affiliation: Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, Minnesota 55455.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Rasmussen
authors.affiliation: Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, Minnesota 55455.
authors.forename: Satyabrata
authors.initials: S
authors.lastname: Das
authors.affiliation: Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, Minnesota 55455.
authors.forename: Camille A
authors.initials: CA
authors.lastname: Walter
authors.affiliation: Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, Minnesota 55455. Electronic address: garry@umn.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Garry
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D019703:Calcineurin / Q000378:metabolism; D019070:Cell Lineage; D004727:Endothelium / Q000166:cytology*; D004742:Enhancer Elements, Genetic; D005260:Female; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: C503994:ER71 protein, mouse; D050778:NFATC Transcription Factors; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D019703:Calcineurin
keywords: ETS transcription factor family; NFAT transcription factor; VEGF; calcineurin; transcription activation; transcription regulation