Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-7-31
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0730-2312
pubmed:author
pubmed:copyrightInfo
(c) 2007 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1198-209
pubmed:dateRevised
2009-8-12
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
pubmed:year
2007
pubmed:articleTitle
Transcriptional regulation of human Oct4 by steroidogenic factor-1.
pubmed:affiliation
Chabiotech Co. Ltd, Seoul, South Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't