OCT4와 SOX2에 의한 인간 Nanog 유전자의 전사 조절
Transcriptional Regulation of Human Nanog Gene by OCT4 and SOX2
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Embryonic stem (ES) cells can self-renew maintaining the undifferentiated state. Self-renewal requires many factors such as OCT4, SOX2, and NANOG. It is previously known that OCT4 and SOX2 can bind to NANOG promoter and support Nanog gene expression in mouse ES cells by the detailed studies using the mouse Nanog promoter. Here, we constructed serial deletion mutant promoter-reporter constructs to investigate the human Nanog gene promoter in detail. The highest promoter activity was obtained in the 0.6 kb (—253/+365) promoter-reporter construct which includes the binding sites of OCT4 and SOX2. To further confirm contribution of OCT4 and SOX2 in Nanog gene expression, we introduced site- directed mutation(s) in the OCT4 and/or SOX2 binding sites of the human Nanog promoter 0.6 kb (—253/+365) and checked the influence of the mutation on the promoter activity using human EC cell line NCCIT. Mutation either in OCT4 binding site or SOX2 binding site significantly reduced the activity of Nanog promoter which directly confirmed that OCT4 and SOX2 binding is essential in human Nanog gene expression.
Abstract
Embryonic stem (ES) cells can self-renew maintaining the undifferentiated state. Self-renewal requires many factors such as OCT4, SOX2, and NANOG. It is previously known that OCT4 and SOX2 can bind to NANOG promoter and support Nanog gene expression in mouse ES cells by the detailed studies using the mouse Nanog promoter. Here, we constructed serial deletion mutant promoter-reporter constructs to investigate the human Nanog gene promoter in detail. The highest promoter activity was obtained in the 0.6 kb (—253/+365) promoter-reporter construct which includes the binding sites of OCT4 and SOX2. To further confirm contribution of OCT4 and SOX2 in Nanog gene expression, we introduced site- directed mutation(s) in the OCT4 and/or SOX2 binding sites of the human Nanog promoter 0.6 kb (—253/+365) and checked the influence of the mutation on the promoter activity using human EC cell line NCCIT. Mutation either in OCT4 binding site or SOX2 binding site significantly reduced the activity of Nanog promoter which directly confirmed that OCT4 and SOX2 binding is essential in human Nanog gene expression.
참고문헌 (22)
- Babaie Y, "Analysis of OCT4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells", Stem Cells, 25, pp.500~510 (2007)
- Chambers I, "Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells", Cell, 113, pp.643~655 (2003)
- Chan KK, "KLF4 and PBX1 directly regulate NANOG expression in human embryonic stem cells", Stem Cells, 27, pp.2114~2125 (2009)
- Evans MJ, "Establishment in culture of pluripotential cells from mouse embryos", Nature, 292, pp.154~156 (1981)
- Han MK, "SIRT1 regulates apoptosis and Nanog expression in mouse embryonic stem cells by controlling p53 subcellular localization", Stem Cells, 2, pp.241~251 (2008)
- Jaenisch R, "Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming", Cell, 132, pp.567~582 (2008)
- Kuroda T, "Octamer and Sox elements are required for transcriptional cis regulation of Nanog gene expression", Mol Cell Biol, 25, pp.2475~2485 (2005)
- Lin T, "p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression", Nat Biotechnol, 7, pp.165~171 (2005)
- Mitsui K, "The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells", Cell, 113, pp.631~642 (2003)
- Niwa H, "Quantitative expression of Oct-3", 4 defines differentiation, dedifferentiation or self-renewal of ES cells, 2000, pp.24, 372~376
- Odorico JS, "Multilineage differentiation from human embryonic stem cell lines", Stem Cells, 19, pp.193~204 (2001)
- Pan G, "Nanog and transcriptional networks in embryonic stem cell pluripotency", Cell Res, 17, pp.42~49 (2007)
- Pan GJ, "Identification of two distinct transactivation domains in the pluripotency sustaining factor nanog", Cell Res, 6, pp.499~502 (2003)
- Reubinoff BE, "Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro", Nat Biotechnol, 18, pp.399~405 (2000)
- Rodda DJ, "Transcriptional regulation of nanog by OCT4 and SOX2", J Biol Chem, 280, pp.24731~24737 (2005)
- Shi W, "Regulation of the pluripotency marker rex-1 by nanog and sox2", J Biol Chem, 281, pp.23319~23325 (2006)
- Shultz WA, "Transcriptional networks in embryonic stem cells and testicular cancer and the definition of epigenetics", Epigenetics, 2, pp.37~42 (2007)
- Silva J, "Nanog promotes transfer of pluripotency after cell fusion", Nature, 441, pp.997~1001 (2006)
- Singh AM, "A heterogeneous expression pattern for Nanog in embryonic stem cells", Stem Cells, 25, pp.2534~2542 (2007)
- Thomson JA, "Embryonic stem cell lines derived from human blastocysts", Science, 282, pp.1145~1147 (1998)
- Torres J, "Nanog maintains pluripotency of mouse embryonic stem cells by inhibiting NF-κB and cooperating with Stat3", Nat Cell Biol, 10, pp.194~201 (2008)
- Yamanaka S, "Strategies and new developments in the generation of patient-specific pluripotent stem cells", Cell Stem Cell, 1, pp.39~49 (2007)