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PMID: 12136102 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nucleic acids research ·Vol. 30 ·No. 14 ·2002-07-15 ·Pages 3202-13

Tomioka M, Nishimoto M, Miyagi S, Katayanagi T, Fukui N, Niwa H, Muramatsu M, Okuda A

Abstract

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.

MeSH Terms
Animals Base Sequence Binding Sites/genetics COS Cells Cell Line Chromosomal Proteins, Non-Histone Cloning, Molecular DNA-Binding Proteins/genetics,metabolism HMGB Proteins Luciferases/genetics,metabolism Macromolecular Substances Mice Mice, Inbred Strains Molecular Sequence Data Nuclear Proteins/genetics,metabolism Octamer Transcription Factor-3 Octamer Transcription Factor-6 Plasmids/genetics Protein Binding Recombinant Fusion Proteins/genetics,metabolism Regulatory Sequences, Nucleic Acid/genetics SOXB1 Transcription Factors Trans-Activators/genetics,metabolism Transcription Factors/genetics,metabolism Transcription, Genetic Transfection Tumor Cells, Cultured
Chemicals
Chromosomal Proteins, Non-Histone DNA-Binding Proteins HMGB Proteins Macromolecular Substances Nuclear Proteins Octamer Transcription Factor-3 Pou3f1 protein, mouse Pou5f1 protein, mouse Recombinant Fusion Proteins SOXB1 Transcription Factors Sox2 protein, mouse Trans-Activators Transcription Factors Utf1 protein, mouse Octamer Transcription Factor-6 Luciferases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Tomioka Mizuho
Division of Developmental Biology, Saitama Medical School Research Center for Genomic Medicine, 1397-1 Yamane Hidaka-City, Saitama 350-1241, Japan.
Nishimoto Masazumi
Miyagi Satoru
Katayanagi Tomoko
Fukui Nobutaka
Niwa Hitoshi
Muramatsu Masami
Okuda Akihiko
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkf435
Published
2002-07-15
Pages
3202-13
Language
English
Region
England
NLM ID
0411011
PMCID
PMC135755
Subset
IM
Databases
GENBANK
AB079241
External Links
PubMed source DOI: 10.1093/nar/gkf435 PMC Full Text View journal details
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