{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:07:51Z","timestamp":1791119271143,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[1999,2,1]],"date-time":"1999-02-01T00:00:00Z","timestamp":917827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002342","name":"Suomalainen Tiedeakatemia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002342","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008376","name":"Helsingin ja Uudenmaan Sairaanhoitopiiri","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008376","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["PL 963380"],"award-info":[{"award-number":["PL 963380"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005615","name":"Beth Israel Deaconess Medical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005615","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA71429-01"],"award-info":[{"award-number":["CA71429-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[1999,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The Tie gene encodes an endothelial cell receptor tyrosine kinase necessary for normal vascular development. The Tie gene promoter targets expression of heterologous genes specifically to endothelial cells in transgenic mice. Here we have characterized the promoter sequences critical for endothelial cell\u2010specific activity in cultured cells and transgenic mice. Progressive deletions and site\u2010directed mutations of the promoter showed that the critical endothelial cell\u2010specific elements are an octamer transcription factor binding site and several Ets binding sites located in two clusters within 300 bp upstream of the major transcription initiation site. Among members of the Ets transcription factor family tested, NERF\u20102 (a novel transcription factor related to the ets factor ELF\u20101), which is expressed in endothelial cells, and ETS2 showed the strongest transactivation of the Tie promoter; ETS1 gave lower levels of stimulation and the other Ets factors gave little or no transactivation. Furthermore, the Tie promoter directed the production of high amounts of human growth hormone into the circulation of transgenic mice. The secreted amounts correlated with transgene copy number, being relatively insensitive to the effects of the transgene integration site. These properties suggest that Tie promoter activity is controlled by endothelial cell Ets factors and that it has potential for use in vectors for endothelial cell\u2010specific gene expression.\u2014Iljin, K., Dube, A., Kontusaari, S., Korhonen, J., Lahtinen, I., Oettgen, P., Alitalo, K. Role of Ets factors in the activity and endothelial cell specificity of the mouse Tie gene promoter.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    13, 377\u2013386 (1999)\n                  <\/jats:p>","DOI":"10.1096\/fasebj.13.2.377","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T04:20:34Z","timestamp":1516854034000},"page":"377-386","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Role of Ets factors in the activity and endothelial cell specificity of the mouse Tie gene promoter"],"prefix":"10.1096","volume":"13","author":[{"given":"KRISTIINA","family":"ILJIN","sequence":"first","affiliation":[{"name":"Molecular\/Cancer Biology Laboratory Haartman Institute Department of Biomedicine University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ANTOINISE","family":"DUBE","sequence":"additional","affiliation":[{"name":"NEB Bone and Joint Institute Beth Israel Deaconess Medical Center Harvard Institutes of Medicine  Boston Massachusetts 02115 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SIRPA","family":"KONTUSAARI","sequence":"additional","affiliation":[{"name":"Biocenter Oulu Department of Biochemistry University of Oulu  Linnanmaa 90570 Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JAANA","family":"KORHONEN","sequence":"additional","affiliation":[{"name":"Molecular\/Cancer Biology Laboratory Haartman Institute Department of Biomedicine University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ISTO","family":"LAHTINEN","sequence":"additional","affiliation":[{"name":"Molecular\/Cancer Biology Laboratory Haartman Institute Department of Biomedicine University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PETER","family":"OETTGEN","sequence":"additional","affiliation":[{"name":"NEB Bone and Joint Institute Beth Israel Deaconess Medical Center Harvard Institutes of Medicine  Boston Massachusetts 02115 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KARI","family":"ALITALO","sequence":"additional","affiliation":[{"name":"Molecular\/Cancer Biology Laboratory Haartman Institute Department of Biomedicine University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[1999,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00936.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/21.24.5636"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.2.999"},{"key":"e_1_2_7_5_1","first-page":"895","article-title":"Endothelial specific gene expression directed by the tie gene promoter in vivo.","volume":"129","author":"Korhonen J.","year":"1995","journal-title":"Blood"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.46.27948"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.39.23111"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1242\/dev.121.4.1089","article-title":"Vascular endothelial cell lineage-specific promoter in transgenic mice","volume":"121","author":"Schlaeger T. 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