Transcriptional inhibition of etv2 expression is essential for embryonic cardiac development

• Published in: Developmental biology 2014-09, Vol.393 (1), p.71-83
• Main Authors: Schupp, Marcus-Oliver, Waas, Matthew, Chun, Chang-Zoon, Ramchandran, Ramani
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Basic Helix-Loop-Helix Transcription Factors - genetics; Cardiac disc; Cell Differentiation - genetics; Cell Line; Cell Lineage; Danio rerio; embryogenesis; Embryonic Stem Cells; endothelial cells; Endothelial Cells - cytology; Endothelium, Vascular - cytology; Endothelium, Vascular - embryology; Erythrocytes - cytology; Etv2; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; Gene Silencing; genomics; Heart - embryology; Homeobox Protein Nkx-2.5; introns; loci; Morpholinos - genetics; plasticity; Promoter Regions, Genetic; Proto-Oncogene Proteins - genetics; regulatory sequences; Scl; stem cells; T-Cell Acute Lymphocytic Leukemia Protein 1; Transcription; transcription (genetics); transcription factors; Transcription Factors - genetics; Transcription, Genetic - genetics; Transgenes; Zebrafish; Zebrafish - embryology; Zebrafish - genetics; Zebrafish Proteins - biosynthesis; Zebrafish Proteins - genetics
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2014.06.019

E-twenty six variant 2 (Etv2) transcription factor participates in cardiac, vascular-endothelial and blood cell lineage specification decisions during embryonic development. Previous studies have identified genomic elements in the etv2 locus responsible for vascular endothelial cell specification. Using transgenic analysis in zebrafish, we report here an etv2 proximal promoter fragment that prevents transgene misexpression in myocardial progenitor cells. This inhibition of etv2 expression in the cardiac progenitor population is partly mediated by Scl and Nkx2.5, likely through direct binding to the etv2 promoter, and cis-regulatory elements located in the first and second introns. The results identify an etv2 cis-regulatory mechanism controlling cardiovascular fate choice implying that etv2 participates in a transcriptional network mediating developmental plasticity of endothelial progenitor cells during embryonic development. •On a dynamic cis-regulatory mechanism to restrict etv2 function.•Proximal promoter sequences that prevents etv2 misexpression in cardiac cells.•Scl and nkx2.5 inhibit cardiac etv2 expression.•Nkx2.5׳s role in cardiac repression mechanism is Scl-dependent.•Identification of intronic elements responsible for the etv2 regulation.