rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2007-7-31
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pubmed:abstractText |
Oct4 encodes a transcription factor that is involved in the maintenance of self-renewal in stem cells. Recently, the molecular mechanisms that regulate Oct4 expression have come under investigation. In this study, we demonstrate that the orphan nuclear receptor steroidogenic factor-1 (SF-1) behaves as a transcriptional activator of human Oct4 (hOct4) through direct interaction with a SF-1 binding element in the hOct4 proximal promoter. We found that Oct4 and SF-1 were co-expressed in undifferentiated human embryonal carcinoma NCCIT cells and downregulated during retinoic acid-mediated differentiation. We examined the functional role played by SF-1 in regulation of hOct4 transcription using a luciferase reporter assay and Western blot analysis. Overexpression of SF-1 increased up to about threefold hOct4 promoter activity and endogenous hOct4 protein expression. Sequence analysis of the hOct4 promoter revealed that the transcriptional activity was closely linked to Conserved Regions 1 (CR1) and 2 (CR2), which contain three putative SF-1-binding sites (1st, 2nd, and 3rd SF-1). Binding assays and mutagenesis of binding sites indicated that the 1st and 2nd SF-1 elements (in CR1 and CR2, respectively) might be important cis-regulatory elements in hOct4 promoter activity. However, differences in response to SF-1 overexpression between wild-type and mutant hOct4 promoters revealed that the 1st SF-1 element is the key binding site for SF-1-mediated transcriptional activation. Thus, our data indicate that SF-1 plays a crucial role in the regulation of hOct4 transcription through direct binding to the 1st SF-1 in CR1 of the hOct4 proximal promoter.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NR5A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Octamer Transcription Factor-3,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Steroidogenic Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin,
http://linkedlifedata.com/resource/pubmed/chemical/steroidogenic factor 1, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0730-2312
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pubmed:author |
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pubmed:copyrightInfo |
(c) 2007 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1198-209
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pubmed:dateRevised |
2009-8-12
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pubmed:meshHeading |
pubmed-meshheading:17226773-Animals,
pubmed-meshheading:17226773-Base Sequence,
pubmed-meshheading:17226773-Binding Sites,
pubmed-meshheading:17226773-Cell Differentiation,
pubmed-meshheading:17226773-Cell Line, Tumor,
pubmed-meshheading:17226773-Conserved Sequence,
pubmed-meshheading:17226773-Down-Regulation,
pubmed-meshheading:17226773-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17226773-Homeodomain Proteins,
pubmed-meshheading:17226773-Humans,
pubmed-meshheading:17226773-Mice,
pubmed-meshheading:17226773-Molecular Sequence Data,
pubmed-meshheading:17226773-Octamer Transcription Factor-3,
pubmed-meshheading:17226773-Promoter Regions, Genetic,
pubmed-meshheading:17226773-Protein Binding,
pubmed-meshheading:17226773-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:17226773-Steroidogenic Factor 1,
pubmed-meshheading:17226773-Trans-Activators,
pubmed-meshheading:17226773-Transcription, Genetic,
pubmed-meshheading:17226773-Transcription Factors,
pubmed-meshheading:17226773-Transcriptional Activation,
pubmed-meshheading:17226773-Tretinoin
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pubmed:year |
2007
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pubmed:articleTitle |
Transcriptional regulation of human Oct4 by steroidogenic factor-1.
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pubmed:affiliation |
Chabiotech Co. Ltd, Seoul, South Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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