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PMID: 10409735 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The gene for the embryonic stem cell coactivator UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2.

Molecular and cellular biology ·Vol. 19 ·No. 8 ·1999-08-00 ·Pages 5453-65

Nishimoto M, Fukushima A, Okuda A, Muramatsu M

Abstract

UTF1 is a transcriptional coactivator which has recently been isolated and found to be expressed mainly in pluripotent embryonic stem (ES) cells (A. Okuda, A. Fukushima, M. Nishimoto, et al., EMBO J. 17:2019-2032, 1998). To gain insight into the regulatory network of gene expression in ES cells, we have characterized the regulatory elements governing UTF1 gene expression. The results indicate that the UTF1 gene is one of the target genes of an embryonic octamer binding transcription factor, Oct-3/4. UTF1 expression is, like the FGF-4 gene, regulated by the synergistic action of Oct-3/4 and another embryonic factor, Sox-2, implying that the requirement for Sox-2 by Oct-3/4 is not limited to the FGF-4 enhancer but is rather a general mechanism of activation for Oct-3/4. Our biochemical analyses, however, also reveal one distinct difference between these two regulatory elements: unlike the FGF-4 enhancer, the UTF1 regulatory element can, by its one-base difference from the canonical octamer-binding sequence, selectively recruit the complex comprising Oct-3/4 and Sox-2 and preclude the binding of the transcriptionally inactive complex containing Oct-1 or Oct-6. Furthermore, our analyses reveal that these properties are dictated by the unique ability of the Oct-3/4 POU-homeodomain that recognizes a variant of the Octamer motif in the UTF1 regulatory element.

MeSH Terms
Animals Base Sequence Binding Sites Cell Differentiation Chromosomal Proteins, Non-Histone DNA/metabolism DNA-Binding Proteins/metabolism Embryo, Mammalian/cytology Gene Expression Regulation, Developmental Genes Genes, Regulator HMGB Proteins HeLa Cells Humans Macromolecular Substances Mice Mice, Inbred BALB C Molecular Sequence Data Nuclear Proteins/metabolism Octamer Transcription Factor-3 Organoids SOXB1 Transcription Factors Sequence Alignment Stem Cells/metabolism Trans-Activators/genetics Transcription Factors/metabolism Transcription, Genetic Transfection
Chemicals
Chromosomal Proteins, Non-Histone DNA-Binding Proteins HMGB Proteins Macromolecular Substances Nuclear Proteins Octamer Transcription Factor-3 POU5F1 protein, human Pou5f1 protein, mouse SOX2 protein, human SOXB1 Transcription Factors Sox2 protein, mouse Trans-Activators Transcription Factors UTF1 protein, human Utf1 protein, mouse DNA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Nishimoto M
Department of Biochemistry, Saitama Medical School, Iruma-gun, Saitama 350-0495, Japan.
Fukushima A
Okuda A
Muramatsu M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.8.5453
Published
1999-08-00
Pages
5453-65
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84387
Subset
IM
Databases
GENBANK
AB017360
External Links
PubMed source DOI: 10.1128/MCB.19.8.5453 PMC Full Text View journal details
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