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The transcriptional regulator CCCTC-binding factor limits oxidative stress in endothelial cells.
Roy, Anna R; Ahmed, Abdalla; DiStefano, Peter V; Chi, Lijun; Khyzha, Nadiya; Galjart, Niels; Wilson, Michael D; Fish, Jason E; Delgado-Olguín, Paul.
Afiliación
  • Roy AR; From the Translational Medicine Research Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
  • Ahmed A; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
  • DiStefano PV; From the Translational Medicine Research Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
  • Chi L; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
  • Khyzha N; Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario M5G 2C4, Canada.
  • Galjart N; From the Translational Medicine Research Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
  • Wilson MD; Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario M5G 2C4, Canada.
  • Fish JE; Department of Cell Biology and Genetics, Erasmus Medical Center, Rotterdam 3015 CN, The Netherlands.
  • Delgado-Olguín P; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
J Biol Chem ; 293(22): 8449-8461, 2018 06 01.
Article en En | MEDLINE | ID: mdl-29610276
The CCCTC-binding factor (CTCF) is a versatile transcriptional regulator required for embryogenesis, but its function in vascular development or in diseases with a vascular component is poorly understood. Here, we found that endothelial Ctcf is essential for mouse vascular development and limits accumulation of reactive oxygen species (ROS). Conditional knockout of Ctcf in endothelial progenitors and their descendants affected embryonic growth, and caused lethality at embryonic day 10.5 because of defective yolk sac and placental vascular development. Analysis of global gene expression revealed Frataxin (Fxn), the gene mutated in Friedreich's ataxia (FRDA), as the most strongly down-regulated gene in Ctcf-deficient placental endothelial cells. Moreover, in vitro reporter assays showed that Ctcf activates the Fxn promoter in endothelial cells. ROS are known to accumulate in the endothelium of FRDA patients. Importantly, Ctcf deficiency induced ROS-mediated DNA damage in endothelial cells in vitro, and in placental endothelium in vivo Taken together, our findings indicate that Ctcf promotes vascular development and limits oxidative stress in endothelial cells. These results reveal a function for Ctcf in vascular development, and suggest a potential mechanism for endothelial dysfunction in FRDA.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ataxia de Friedreich / Endotelio Vascular / Regulación de la Expresión Génica / Especies Reactivas de Oxígeno / Estrés Oxidativo / Embrión de Mamíferos / Factor de Unión a CCCTC Límite: Animals / Female / Humans / Male Idioma: En Revista: J Biol Chem Año: 2018 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ataxia de Friedreich / Endotelio Vascular / Regulación de la Expresión Génica / Especies Reactivas de Oxígeno / Estrés Oxidativo / Embrión de Mamíferos / Factor de Unión a CCCTC Límite: Animals / Female / Humans / Male Idioma: En Revista: J Biol Chem Año: 2018 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos