TRANSCRIPTIONAL REGULATION OF NEURON-SPECIFIC GENES AND MODULATION BY DRUGSNOVEL TRANSCRIPRION FACTORS INVOLVED IN NEURAL DIFFERENTIATION AND MEMORY

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Neuropeptide Y (NPY) is a cortransmitter of sympathetic neurons and is expressed abundantly in the central nervous system. By using the rat NPY gene, the regulatory mechanism of transcription of the neuron-specific genes has been studied and the transcriptional factors have been explored. So far we have identified the unique enhancer elements, such as nerve growth factor (NGF) response element (NGFRE) and calcium/calmodulin-dependent kinase response element (CaRE). By the Southwestern method, we have cloned the novel transcription factors whith are bound to these unique, evolutionally-conserved, enhancer elements. It is likely that these factors are important for transcriptional activation through NGFRE and CaRE.In 1996 we have indentified NDF1 (NGFRE-DNA binding factor-1) as a NGFRE-binding protein. This protein is a 26kDa capsicin-binding protein and has a repressive function on the NPY gene transcription. NDF1 has also suppressive action on NGF-induced neuronal differentiation of clonal PC12 cells. NDF1 seemed to be a suppressor of neuronal differentiation of sympathetic neurons. The neuroactive substrances such as capsicin may regulate this transcription factor.In 1997 the distribution of NDF1 mRNA was investigated in the nervous system during outogeny by in situ hybridization. In adult rat 26kDa NDF1 mRNA was distributed widely in the central and peripheral nervous system in a cell-specific manner. In contrast in embryonic animals NDF1 mRNA was also expressed in the extraneural tissues, such as bone marrow, liver, and kidney. These date suggested that NDF1 has additional function in the differntiation of the various organ-specific cells.