NGF-dependent and tissue-specific transcription of vgf is regulated by a CREB-p300 and bHLH factor interaction

Neurotrophins support neuronal survival, development, and plasticity through processes requiring gene expression. We studied how vgf target gene transcription is mediated by a critical promoter region containing E box, CCAAT and CRE sites. The p300 acetylase was present in two distinct protein complexes bound to this region. One complex, containing HEB (ubiquitary bHLH), bound the promoter in non neuronal cells and was involved in repressing vgf expression. Neurotrophin dependent transcription was mediated by the second complex, specific for neuronal cells, which included CREB and Mash1 (neurospecific bHLH), bound the CCAAT motif, and was target of neurotrophin signalling. The interaction, mediated by p300, of different transcription factors may add specificity to the neurotrophin response.