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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
17
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pubmed:dateCreated |
1997-5-21
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pubmed:databankReference |
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pubmed:abstractText |
Thrombopoietin (TPO), the ligand for c-Mpl, is a cytokine that regulates megakaryocyte growth and development. We have cloned the 5'-flanking region of the human TPO gene and analyzed its promoter activity. The human TPO gene promoter lacks a TATA box and directs transcription initiation at multiple sites over a 50-nucleotide region. Transient expression in a human liver cell line (PLC) of promoter fragment-luciferase reporter gene constructs containing a series of 5'-truncated sequences or site-directed mutations identified a sequence 5'-ACTTCCG-3' from -69 to -63 as a positive cis-acting element for high level expression of TPO gene. This sequence contains a core motif (C/A)GGA(A/T) for Ets family proteins in the noncoding strand. Gel mobility shift assays performed with nuclear protein from PLC cells identified a DNA binding protein(s) specific for the element. Anti-E4TF1-60(GABPalpha) or anti-E4TF1-53/47(GABPbeta) antibodies supershifted the complex in gel shift assay. Furthermore, co-expression of E4TF1-60 and E4TF1-53/47 squelched TPO gene expression in PLC and HepG2 cells. It is concluded that Ets family transcription factor E4TF1(GABPalpha/beta), an ubiquitously expressed protein, is required for high level expression of the TPO gene in liver.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
272
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
11361-8
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9111044-Base Sequence,
pubmed-meshheading:9111044-Cloning, Molecular,
pubmed-meshheading:9111044-Consensus Sequence,
pubmed-meshheading:9111044-GA-Binding Protein Transcription Factor,
pubmed-meshheading:9111044-Genes, Reporter,
pubmed-meshheading:9111044-Humans,
pubmed-meshheading:9111044-Molecular Sequence Data,
pubmed-meshheading:9111044-Promoter Regions, Genetic,
pubmed-meshheading:9111044-Protein Binding,
pubmed-meshheading:9111044-Proto-Oncogene Proteins,
pubmed-meshheading:9111044-Proto-Oncogene Proteins c-ets,
pubmed-meshheading:9111044-Recombinant Fusion Proteins,
pubmed-meshheading:9111044-Sequence Analysis, DNA,
pubmed-meshheading:9111044-Sequence Deletion,
pubmed-meshheading:9111044-Thrombopoietin,
pubmed-meshheading:9111044-Transcription, Genetic,
pubmed-meshheading:9111044-Transcription Factors,
pubmed-meshheading:9111044-Tumor Cells, Cultured
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pubmed:year |
1997
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pubmed:articleTitle |
Characterization of the human thrombopoietin gene promoter. A possible role of an Ets transcription factor, E4TF1/GABP.
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pubmed:affiliation |
Department of Clinical Chemistry and Laboratory Medicine, Kyushu University, Faculty of Medicine, Fukuoka 812-82, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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