{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:14:57Z","timestamp":1789733697483,"version":"4.0.1"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2014,5,23]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      Cardiovascular health depends on proper development and integrity of blood vessels. Ets variant 2 (Etv2), a member of the E26 transforming\u2013specific family of transcription factors, is essential to initiate a transcriptional program leading to vascular morphogenesis in early mouse embryos. However, endothelial expression of the\n                      <jats:italic>Etv2<\/jats:italic>\n                      gene ceases at midgestation; therefore, vascular development past this stage must continue independent of Etv2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>To identify molecular mechanisms underlying transcriptional regulation of vascular morphogenesis and homeostasis in the absence of Etv2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      Using loss- and gain-of-function strategies and a series of molecular techniques, we identify Friend leukemia integration 1 (\n                      <jats:italic>Fli1<\/jats:italic>\n                      ), another E26 transforming\u2013specific family transcription factor, as a downstream target of Etv2. We demonstrate that Etv2 binds to conserved Ets-binding sites within the promoter region of the\n                      <jats:italic>Fli1<\/jats:italic>\n                      gene and governs\n                      <jats:italic>Fli1<\/jats:italic>\n                      expression. Importantly, in the absence of Etv2 at midgestation, binding of Etv2 at Ets-binding sites in the\n                      <jats:italic>Fli1<\/jats:italic>\n                      promoter is replaced by Fli1 protein itself, sustaining expression of\n                      <jats:italic>Fli1<\/jats:italic>\n                      as well as selective Etv2-regulated endothelial genes to promote endothelial cell survival and vascular integrity. Consistent with this, we report that Fli1 binds to the conserved Ets-binding sites within promoter and enhancer regions of other Etv2-regulated endothelial genes, including\n                      <jats:italic>Tie2<\/jats:italic>\n                      , to control their expression at and beyond midgestation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      We have identified a novel positive feed-forward regulatory loop in which Etv2 activates expression of genes involved in vasculogenesis, including\n                      <jats:italic>Fli1<\/jats:italic>\n                      . Once the program is activated in early embryos, Fli1 then takes over to sustain the process in the absence of Etv2.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.1134303145","type":"journal-article","created":{"date-parts":[[2014,4,11]],"date-time":"2014-04-11T23:36:17Z","timestamp":1397259377000},"page":"1690-1699","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":46,"title":["Fli1 Acts Downstream of Etv2 to Govern Cell Survival and Vascular Homeostasis via Positive Autoregulation"],"prefix":"10.1161","volume":"114","author":[{"given":"Md J.","family":"Abedin","sequence":"first","affiliation":[{"name":"From the Department of Internal Medicine (Cardiology) (M.J.A., A.N., N.J., C.E.P., J.M.S., A.F.), University of Texas Southwestern Medical Center, Dallas; Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston (D.K.W.); and Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis (M.J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Nguyen","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (Cardiology) (M.J.A., A.N., N.J., C.E.P., J.M.S., A.F.), University of Texas Southwestern Medical Center, Dallas; Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston (D.K.W.); and Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis (M.J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Jiang","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (Cardiology) (M.J.A., A.N., N.J., C.E.P., J.M.S., A.F.), University of Texas Southwestern Medical Center, Dallas; Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston (D.K.W.); and Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis (M.J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron E.","family":"Perry","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (Cardiology) (M.J.A., A.N., N.J., C.E.P., J.M.S., A.F.), University of Texas Southwestern Medical Center, Dallas; Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston (D.K.W.); and Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis (M.J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Shelton","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (Cardiology) (M.J.A., A.N., N.J., C.E.P., J.M.S., A.F.), University of Texas Southwestern Medical Center, Dallas; Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston (D.K.W.); and Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis (M.J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis K.","family":"Watson","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (Cardiology) (M.J.A., A.N., N.J., C.E.P., J.M.S., A.F.), University of Texas Southwestern Medical Center, Dallas; Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston (D.K.W.); and Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis (M.J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwarul","family":"Ferdous","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (Cardiology) (M.J.A., A.N., N.J., C.E.P., J.M.S., A.F.), University of Texas Southwestern Medical Center, Dallas; Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston (D.K.W.); 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