Interplay of the E box, the cyclic AMP response element, and HTF4/HEB in transcriptional regulation of the neurospecific, neurotrophin-inducible vgf gene

Giuliana Di Rocco, Maria Pennuto, Barbara Illi, Nadia Canu, Gessica Filocamo, Eugenia Trani, Anna Maria Rinaldi, Roberta Possenti, Georgia Mandolesi, M. Isabella Sirinian, Richard Jucker, Andrea Levi, Sergio Nasi

Research output: Contribution to journalArticlepeer-review

Abstract

vgf is a neurotrophin response-specific, developmentally regulated gene that codes for a neurosecretory polypeptide. Its transcription in neuronal cells is selectively activated by the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor, and neurotrophin 3, which induce survival and differentiation, and not by epidermal growth factor. We studied a short region of the rat vgf promoter which is essential for its regulated expression. A cyclic AMP response element (CRE) within this region is necessary for NGF induction of vgf transcription. Two sites upstream of CRE, an E box and a CCAAT sequence, bind nuclear protein complexes and are involved in transcriptional control. The E box has a dual role. It acts as an inhibitor in NIH 3T3 fibroblasts, together with a second E box located downstream, and as a stimulator in the NGF-responsive cell line PC12. By expression screening, we have isolated the cDNA for a basic helix-loop-helix transcription factor, a homolog of the HTF4/HEB E protein, that specifically binds the vgf promoter E box. The E protein was present in various cell lines, including PC12 cells, and was a component of a multiprotein nuclear complex that hinds the promoter in vitro. The E box and CRE cooperate in binding to this complex, which may be an important determinant for neural cell-specific expression.

Original languageEnglish
Pages (from-to)1244-1253
Number of pages10
JournalMolecular and Cellular Biology
Volume17
Issue number3
Publication statusPublished - Mar 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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