Identification of Sox-2 regulatory region which is under the control of Oct-3/4-Sox-2 complex.
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.
Division of Developmental Biology, Saitama Medical School Research Center for Genomic Medicine, 1397-1 Yamane Hidaka-City, Saitama 350-1241, Japan.
Mizuho
M
Tomioka
Masazumi
M
Nishimoto
Satoru
S
Miyagi
Tomoko
T
Katayanagi
Nobutaka
N
Fukui
Hitoshi
H
Niwa
Masami
M
Muramatsu
Akihiko
A
Okuda
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024002:HMGB Proteins; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D050814:Octamer Transcription Factor-3; D050816:Octamer Transcription Factor-6; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D055748:SOXB1 Transcription Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494180:Pou3f1 protein, mouse; C494174:Pou5f1 protein, mouse; D011993:Recombinant Fusion Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C112198:Utf1 protein, mouse; D050816:Octamer Transcription Factor-6; D008156:Luciferases