An initiator element is required for maximal human chorionic somatomammotropin gene promoter and enhancer function

S. W. Jiang, A. R. Shepard, N. L. Eberhardt

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Previous studies have indicated that cell-specific expression of the human chorionic somatomammotropin (hCS) gene may be mediated by a placental- specific enhancer (CSEn). In the current studies, we have analyzed the promoter elements that are required for enhancer and promoter function in choriocarcinoma cells (BeWo). Mutation of both hCS GHF1 sites had no effect on promoter or enhancer activity. In contrast, mutation of the Sp1 site diminished basal and CSEn-stimulated transcription by ≃75% and ≃56%, respectively, indicating that Sp1 was necessary but not sufficient for maximal basal and enhancer-mediated transcription. Deletion and site-specific mutation of the proximal promoter region indicated that the TATA box and an initiator site (InrE) located between nucleotides -15/+1 of the hCS promoter were required for maximal promoter and enhancer function. Mutations of the InrE were associated with reduced basal and enhancer-stimulated activities and altered transcription initiation sites. A protein of 70-kDa mass, that was preferentially expressed in human choriocarcinoma cells (BeWo and JEG- 3), bound specifically to the InrE. The data suggest that an initiator present in high concentrations in placental cells contributes to the control of cell-specific hCS gene expression at the promoter level and is required for maximal enhancer function.

Original languageEnglish (US)
Pages (from-to)3683-3692
Number of pages10
JournalJournal of Biological Chemistry
Volume270
Issue number8
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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