Identification of Sox‐2 regulatory region which is under the control of Oct‐3/4–Sox‐2 complex

• Published in: Nucleic acids research Vol. 30; no. 14; pp. 3202 - 3213
• Main Authors: Tomioka, Mizuho, Nishimoto, Masazumi, Miyagi, Satoru, Katayanagi, Tomoko, Fukui, Nobutaka, Niwa, Hitoshi, Muramatsu, Masami, Okuda, Akihiko
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 15.07.2002; Oxford Publishing Limited (England)
• Subjects: Animals; Base Sequence; Binding Sites - genetics; Cell Line; Chromosomal Proteins, Non-Histone; Cloning, Molecular; COS Cells; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; HMGB Proteins; Luciferases - genetics; Luciferases - metabolism; Macromolecular Substances; Mice; Mice, Inbred Strains; Molecular Sequence Data; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Octamer Transcription Factor-3; Octamer Transcription Factor-6; Plasmids - genetics; Protein Binding; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Regulatory Sequences, Nucleic Acid - genetics; SOXB1 Transcription Factors; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Transfection; Tumor Cells, Cultured
• ISSN: 0305-1048; 1362-4962; 1362-4962
• DOI: 10.1093/nar/gkf435

Sox‐2 is a transcriptional cofactor expressed in embryonic stem (ES) cells as well as in neuronal cells. It has been demonstrated that Sox‐2 plays an important role in supporting gene expression in ES cells, especially by forming a complex with embryonic Octamer factor, Oct‐3/4. Here, we have analyzed the regulatory regions of the Sox‐2 gene and identified two enhancers which stimulate transcription in ES cells as well as in embryonal carcinoma cells. These regulatory regions, which we termed Sox regulatory regions (SRR) 1 and 2, exert their function specifically when cells are in an undifferentiated state. Interestingly, like the regulatory elements of FGF‐4 and UTF1 genes, combinatorial action of Octamer and Sox‐2 binding sites support the SRR2 activity. However, biochemical analyses reveal that, due to the unique sequence and/or its organization, the SRR2 bears distinct characteristics from those of FGF‐4 and UTF1 regulatory elements. That is, unlike the FGF‐4 gene enhancer, the SRR2 precludes the binding of the Oct‐1–Sox‐2 complex. The difference between the SRR2 and UTF1 regulatory element is in the ability of SRR2 to recruit the Oct‐6–Sox‐2 complex as well as the Oct‐3/4–Sox‐2 complex. Co‐transfection analyses confirm that both complexes are able to stimulate transcription through the SRR2 element.