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

被引:29
作者
DiRocco, G
Pennuto, M
Illi, B
Canu, N
Filocamo, G
Trani, E
Rinaldi, AM
Possenti, R
Mandolesi, G
Sirinian, MI
Jucker, R
Levi, A
Nasi, S
机构
[1] UNIV ROMA LA SAPIENZA,CNR,CTR ACIDI NUCL,I-00185 ROME,ITALY
[2] CNR,IST NEUROBIOL,I-00156 ROME,ITALY
关键词
D O I
10.1128/MCB.17.3.1244
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 binds 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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页码:1244 / 1253
页数:10
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