A GC-Rich Element Confers Epidermal Growth Factor Responsiveness to Transcription from the Gastrin Promoter

Juanita L. Merchant, Barbara Demediuk, Stephen J. Brand

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

Epidermal growth factor (EGF) and transforming growth factor a are important determinants of mucosal integrity in the gastrointestinal tract, and they act both directly and indirectly to prevent ulceration in the stomach. Consistent with this physiological role, EGF stimulates transcription of gastrin, a peptide hormone which regulates gastric acid secretion and mucosal growth. EGF stimulation of gastrin transcription is mediated by a GC-rich gastrin EGF response element (gERE) (GGGGCGGGGTGGGGGG) which lies between -54 and -68 in the human gastrin promoter. The gERE sequence also confers weaker responsiveness to phorbol ester stimulation. The gERE sequence differs from previously described EGF response elements. The gERE DNA sequence specifically interacts with a GH4 DNA-binding protein distinct from previously described transcription factors (Egr-1 and AP2) which bind GC-rich sequences and mediate transcriptional activation by growth factors. Furthermore, the gERE element does not bind the Sp1 transcription factor even though the gERE sequence contains a high-affinity Sp1-binding site (GGCGGG).

Original languageEnglish (US)
Pages (from-to)2686-2696
Number of pages11
JournalMolecular and cellular biology
Volume11
Issue number5
StatePublished - May 1991
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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