Linked Life Data

15652157

Source:http://linkedlifedata.com/resource/pubmed/id/15652157

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-1-17
pubmed:abstractText
The human reduced folate carrier (hRFC) is ubiquitously but differentially expressed in human tissues and its levels are regulated by up to six alternatively spliced non-coding regions (designated A1/A2, A, B, C, D, and E) and by at least four promoters. By transient transfections of HepG2 human hepatoma cells with 5' and 3' deletion constructs spanning 2883 bp of upstream sequence, a transcriptionally important region was localized to within 177 bp flanking the transcriptional start sites for exon C. By gel shift and chromatin immunoprecipitation assays, Sp1 and C/EBP beta transcription factors were found to bind consensus elements (GC-box, CCAAT-box) within this region. The functional importance of these elements was confirmed by transient tranfections of HepG2 cells with hRFC-C reporter constructs in which these elements were mutated, and by co-transfections of Drosophila SL-2 cells with wild-type hRFC-C promoter and expression constructs for Sp1 and C/EBP beta. Whereas both Sp1 and C/EBP beta transactivated hRFC-C promoter activity, C/EBP alpha and gamma were transcriptionally inert. Sp1 combined with C/EBP beta resulted in a synergistic transactivation. In HepG2 cells, transfections with Sp1 and C/EBP beta both increased endogenous levels of hRFC-C transcripts. By 3' deletion analysis, a repressor sequence was localized to within 71 bp flanking the minimal promoter. On gel shifts, a novel transcriptional repressor was localized to within 30 bp. Collectively, these results identify transcriptionally important regions in the hRFC-C minimal promoter that include a GC-box and CCAAT-box, and suggest that cooperative interactions between Sp1 and C/EBP beta are essential for hRFC-C transactivation. Another possible factor in the tissue-specific regulation of the hRFC-C region involves the downstream repressor flanking the minimal promoter.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
1727
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
45-57
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15652157-Animals, pubmed-meshheading:15652157-Base Sequence, pubmed-meshheading:15652157-CCAAT-Binding Factor, pubmed-meshheading:15652157-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:15652157-Cells, Cultured, pubmed-meshheading:15652157-Chromatin Immunoprecipitation, pubmed-meshheading:15652157-Drosophila, pubmed-meshheading:15652157-Gene Expression Regulation, pubmed-meshheading:15652157-Humans, pubmed-meshheading:15652157-Membrane Transport Proteins, pubmed-meshheading:15652157-Molecular Sequence Data, pubmed-meshheading:15652157-Promoter Regions, Genetic, pubmed-meshheading:15652157-Reduced Folate Carrier Protein, pubmed-meshheading:15652157-Sp1 Transcription Factor, pubmed-meshheading:15652157-Transcription, Genetic, pubmed-meshheading:15652157-Transcription Factor CHOP, pubmed-meshheading:15652157-Transcription Factors, pubmed-meshheading:15652157-Transcriptional Activation, pubmed-meshheading:15652157-Transfection, pubmed-meshheading:15652157-Tumor Cells, Cultured
pubmed:year
2005
pubmed:articleTitle
Transcriptional regulation of the human reduced folate carrier promoter C: synergistic transactivation by Sp1 and C/EBP beta and identification of a downstream repressor.
pubmed:affiliation
Department of Pharmacology, Wayne State University, School of Medicine, Detroit, MI, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.