Early growth response protein 1 acts as an activator of SOX18 promoter
Апстракт
Sex-determining region Y box 18 (Sox18/SOX18) gene is an important regulator of vascular development playing a role in endothelial cell specification or differentiation, angiogenesis and atherogenesis. The aim of this study was to perform comprehensive functional characterization of the human SOX18 promoter, including determination of transcription start point (tsp) and identification of control elements involved in the regulation of SOX18 gene expression, with an emphasis on angiogenesis-related transcription factors. Analyses were performed in HeLa cells, representing a tumor cell line, and in EA.hy926 cells used as an endothelial model system. We have determined unique tsp of SOX18 gene, located 172 nucleotides upstream from ATG codon. Further, we have shown that SOX18 promoter region, -726 to -89 by relative to tsp, contains positive cis-regulatory element(s) that stimulates SOX18 promoter activity, while region -89 to + 166 represents the minimal promoter. Within this region we ha...ve recognized the presence of essential element(s), positioned from -89 to +29, which harbors cluster of three putative early growth response 1 (EGR1) binding sites. By in vitro binding assays and functional analyses we have shown that these three putative binding sites are functionally relevant and sufficient for EGR1-induced SOX18 transcription. Mutations of these binding sites significantly impaired activity of the SOX18 promoter, particularly in EA.hy926 cells, indicating the importance of these regulatory elements for SOX18 promoter activity in endothelial setting. By data presented in this study, we have established SOX18 as a novel target gene regulated by EGR1 transcription factor, thus providing the first functional link between two transcription factors previously shown to be involved in the control of angiogenesis.
Кључне речи:
transcription, genetic / SOX18 protein, human / promoter regions, genetic / neovascularization, physiologic / endothelial cells / early growth response protein 1Извор:
Experimental and Molecular Medicine, 2010, 42, 2, 132-142Издавач:
- Nature Publishing Group, New York
Финансирање / пројекти:
- Изучавање регулације експресије и функције хуманих SOX гена (RS-MESTD-MPN2006-2010-143028)
- International Centre for Genetic Engineering and Biotechnology [CRP/YUG 07-01]
DOI: 10.3858/emm.2010.42.2.015
ISSN: 1226-3613
WoS: 000275039300007
Scopus: 2-s2.0-77649231088
Колекције
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Petrović, Isidora AU - Kovačević Grujičić, Nataša AU - Stevanović, Milena PY - 2010 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/415 AB - Sex-determining region Y box 18 (Sox18/SOX18) gene is an important regulator of vascular development playing a role in endothelial cell specification or differentiation, angiogenesis and atherogenesis. The aim of this study was to perform comprehensive functional characterization of the human SOX18 promoter, including determination of transcription start point (tsp) and identification of control elements involved in the regulation of SOX18 gene expression, with an emphasis on angiogenesis-related transcription factors. Analyses were performed in HeLa cells, representing a tumor cell line, and in EA.hy926 cells used as an endothelial model system. We have determined unique tsp of SOX18 gene, located 172 nucleotides upstream from ATG codon. Further, we have shown that SOX18 promoter region, -726 to -89 by relative to tsp, contains positive cis-regulatory element(s) that stimulates SOX18 promoter activity, while region -89 to + 166 represents the minimal promoter. Within this region we have recognized the presence of essential element(s), positioned from -89 to +29, which harbors cluster of three putative early growth response 1 (EGR1) binding sites. By in vitro binding assays and functional analyses we have shown that these three putative binding sites are functionally relevant and sufficient for EGR1-induced SOX18 transcription. Mutations of these binding sites significantly impaired activity of the SOX18 promoter, particularly in EA.hy926 cells, indicating the importance of these regulatory elements for SOX18 promoter activity in endothelial setting. By data presented in this study, we have established SOX18 as a novel target gene regulated by EGR1 transcription factor, thus providing the first functional link between two transcription factors previously shown to be involved in the control of angiogenesis. PB - Nature Publishing Group, New York T2 - Experimental and Molecular Medicine T1 - Early growth response protein 1 acts as an activator of SOX18 promoter EP - 142 IS - 2 SP - 132 VL - 42 DO - 10.3858/emm.2010.42.2.015 ER -
@article{ author = "Petrović, Isidora and Kovačević Grujičić, Nataša and Stevanović, Milena", year = "2010", abstract = "Sex-determining region Y box 18 (Sox18/SOX18) gene is an important regulator of vascular development playing a role in endothelial cell specification or differentiation, angiogenesis and atherogenesis. The aim of this study was to perform comprehensive functional characterization of the human SOX18 promoter, including determination of transcription start point (tsp) and identification of control elements involved in the regulation of SOX18 gene expression, with an emphasis on angiogenesis-related transcription factors. Analyses were performed in HeLa cells, representing a tumor cell line, and in EA.hy926 cells used as an endothelial model system. We have determined unique tsp of SOX18 gene, located 172 nucleotides upstream from ATG codon. Further, we have shown that SOX18 promoter region, -726 to -89 by relative to tsp, contains positive cis-regulatory element(s) that stimulates SOX18 promoter activity, while region -89 to + 166 represents the minimal promoter. Within this region we have recognized the presence of essential element(s), positioned from -89 to +29, which harbors cluster of three putative early growth response 1 (EGR1) binding sites. By in vitro binding assays and functional analyses we have shown that these three putative binding sites are functionally relevant and sufficient for EGR1-induced SOX18 transcription. Mutations of these binding sites significantly impaired activity of the SOX18 promoter, particularly in EA.hy926 cells, indicating the importance of these regulatory elements for SOX18 promoter activity in endothelial setting. By data presented in this study, we have established SOX18 as a novel target gene regulated by EGR1 transcription factor, thus providing the first functional link between two transcription factors previously shown to be involved in the control of angiogenesis.", publisher = "Nature Publishing Group, New York", journal = "Experimental and Molecular Medicine", title = "Early growth response protein 1 acts as an activator of SOX18 promoter", pages = "142-132", number = "2", volume = "42", doi = "10.3858/emm.2010.42.2.015" }
Petrović, I., Kovačević Grujičić, N.,& Stevanović, M.. (2010). Early growth response protein 1 acts as an activator of SOX18 promoter. in Experimental and Molecular Medicine Nature Publishing Group, New York., 42(2), 132-142. https://doi.org/10.3858/emm.2010.42.2.015
Petrović I, Kovačević Grujičić N, Stevanović M. Early growth response protein 1 acts as an activator of SOX18 promoter. in Experimental and Molecular Medicine. 2010;42(2):132-142. doi:10.3858/emm.2010.42.2.015 .
Petrović, Isidora, Kovačević Grujičić, Nataša, Stevanović, Milena, "Early growth response protein 1 acts as an activator of SOX18 promoter" in Experimental and Molecular Medicine, 42, no. 2 (2010):132-142, https://doi.org/10.3858/emm.2010.42.2.015 . .