The regulation of COUP-TFII gene expression by Ets-1 is enhanced by the steroid receptor co-activators.
Recent phenotypic analysis of orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) [NR2F2] knockout mice shows that COUP-TFII is involved in the angiogenic process in the developing embryos. Since Ets-1 expression is also correlated with angiogenesis, and both Ets-1 and COUP-TFII mRNA are present in mesenchymal cells, we have sought to determine whether Ets-1 is a potential regulator of COUP-TFII gene expression. For this purpose, we performed transient transfection experiments using a luciferase reporter construct containing the mouse COUP-TFII promoter. We found that the COUP-TFII promoter activity is indeed regulated by Ets-1. We have identified two identical inverted potential ETS-binding sites located 47 nucleotides downstream of the start site. Mutation of both sites reduced the ability of Ets-1 to enhance the COUP-TFII promoter activity. Furthermore, other members of the ETS family such as Ets-2 or ETV1 are also potent regulators of the COUP-TFII promoter. Finally, the induction of the COUP-TFII gene is strongly enhanced by the expression of steroid receptor co-activator factors through a direct interaction with Ets-1. These results indicate that COUP-TFII is a potential downstream target of Ets-1 and it may partially mediate the Ets-1 function in angiogenesis.
Petit
Fabrice G
FG
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Salas
Ramiro
R
Tsai
Ming-Jer
MJ
Tsai
Sophia Y
SY
D000818:Animals; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D011987:Receptors, Steroid / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*
D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011987:Receptors, Steroid; D014157:Transcription Factors; C494041:ETS1 protein, human; C494042:Ets1 protein, mouse; C497587:Nr2f2 protein, mouse; C095569:NR2F2 protein, human