Influence of a cap site element on tissue-restricted expression of the glycoprotein hormone α-subunit gene

G. Stanley Cox, Wanfen Xiong

Research output: Contribution to journalArticle

Abstract

Little is known of the transcriptional regulators important for expression of the glycoprotein hormone α-subunit (GPHα) gene in nonendocrine tumors, which secrete free α-subunit at an incidence of 25-80%. Consequently, attempts were made to define cis-regulatory elements and their cognate trans-acting factors that modulate promoter activity in epithelial cell types that do not normally express the glycoprotein hormones. DNA-mediated transient expression of promoter-reporter constructs was used to identify a novel negative regulatory element located at the GPHα gene transcription start site. Mutagenesis of this element produced a 2- to 10-fold increase in promoter activity, depending on the particular mutation and the transfected tumor cell line. Electrophoretic mobility shift analysis detected a protein that binds specifically to a DNA motif encompassing the cap site. It was present at different levels in a variety of cell types. Significantly, the degree to which activity of the wild-type promoter was suppressed relative to that of the mutant promoter was proportional to the level of cap site binding protein in the collection of cell lines examined. These results indicate that a negative regulatory element centered at the GPHα gene cap site and its cognate DNA-binding protein make a significant contribution to the production of α-subunit in a variety of tumor tissues. A detailed understanding of this cis/trans pair may further suggest a mechanism to explain, at least in part, how this gene becomes activated in nonendocrine tumors.

Original languageEnglish (US)
Pages (from-to)752-759
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume260
Issue number3
DOIs
StatePublished - Jul 14 1999

Fingerprint

Tumors
Glycoproteins
Genes
Hormones
Tissue
RNA Cap-Binding Proteins
Cells
Neoplasms
Electrophoretic mobility
Mutagenesis
Nucleotide Motifs
Trans-Activators
Transcription Initiation Site
DNA
DNA-Binding Proteins
Tumor Cell Line
Carrier Proteins
Epithelial Cells
Cell Line
Mutation

Keywords

  • Cap site element
  • Chorionic gonadotropin
  • Gene regulation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Influence of a cap site element on tissue-restricted expression of the glycoprotein hormone α-subunit gene. / Cox, G. Stanley; Xiong, Wanfen.

In: Biochemical and Biophysical Research Communications, Vol. 260, No. 3, 14.07.1999, p. 752-759.

Research output: Contribution to journalArticle

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