Interplay of the E Box, the Cyclic AMP Response Element, and HTF4/HEB in Transcriptional Regulation of the Neurospecific, Neurotrophin-Inducible vgf Gene†

  • Di Rocco G
  • Pennuto M
  • Illi B
  • et al.
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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.

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Di Rocco, G., Pennuto, M., Illi, B., Canu, N., Filocamo, G., Trani, E., … Nasi, S. (1997). Interplay of the E Box, the Cyclic AMP Response Element, and HTF4/HEB in Transcriptional Regulation of the Neurospecific, Neurotrophin-Inducible vgf Gene†. Molecular and Cellular Biology, 17(3), 1244–1253. https://doi.org/10.1128/mcb.17.3.1244

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