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Differential roles for ETS, CREB, and EGR binding sites in mediating VEGF receptor 1 expression in vivo.
Jin, Enjing; Liu, Ju; Suehiro, Jun-Ichi; Yuan, Lei; Okada, Yoshiaki; Nikolova-Krstevski, Vesna; Yano, Kiichiro; Janes, Lauren; Beeler, David; Spokes, Katherine C; Li, Dan; Regan, Erzsébet; Shih, Shou-Ching; Oettgen, Peter; Minami, Takashi; Aird, William C.
Afiliação
  • Jin E; The Center for Vascular Biology Research and Division of Molecular and Vascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Blood ; 114(27): 5557-66, 2009 Dec 24.
Article em En | MEDLINE | ID: mdl-19822898
Vascular endothelial growth factor receptor 1 (VEGFR1) is a marker for endothelial-specific gene expression. We previously reported that the human VEGFR1 promoter (between -748 and +284) contains information for expression in the intact endothelium of transgenic mice. The objective of this study was to dissect the cis-regulatory elements underlying VEGFR1 promoter activity in vitro and in vivo. In primary endothelial cells, binding sites for E74-like factor 1 (ELF-1; between -49 and -52), cyclic adenosine monophosphate response element binding (CREB; between -74 and -81), and early growth response factor 1/3 (EGR-1/3; between -16 to -25) were shown to play a positive role in gene transcription, whereas a putative E26 transformation-specificsequence (ETS) motif between -36 and -39 had a net negative effect on promoter activity. When targeted to the Hprt locus of mice, mutations of the ELF-1 binding site and the CRE element reduced promoter activity in the embryonic vasculature and resulted in a virtual loss of expression in adult endothelium. Postnatally, the EGR binding site mutant displayed significantly reduced promoter activity in a subset of vascular beds. In contrast, mutation of the -39 ETS site resulted in increased LacZ staining in multiple vascular beds. Together, these results provide new insights into the transcriptional regulatory mechanisms of VEGFR1.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Proteínas Nucleares / Regiões Promotoras Genéticas / Receptor 1 de Fatores de Crescimento do Endotélio Vascular / Proteína de Ligação a CREB / Fatores de Transcrição de Resposta de Crescimento Precoce Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2009 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Proteínas Nucleares / Regiões Promotoras Genéticas / Receptor 1 de Fatores de Crescimento do Endotélio Vascular / Proteína de Ligação a CREB / Fatores de Transcrição de Resposta de Crescimento Precoce Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2009 Tipo de documento: Article