[Gene regulation involved in the formation of long-term memory]

My former research focused on silk fibroin gene transcription. The in vivo transcription initiation site of the fibroin gene, which is similar to the site corresponding to the 5'-terminal of mature fibroin mRNA, was determined. By developing a cell-free transcription system prepared from silk glands, it was found that the upstream region of the fibroin gene is responsible for efficient transcription initiation, which has enhancer-like features. More recent research has switched my focus to cellular neurobiology to understand the molecular mechanisms of long-term memory at the level of gene expression in terms of cell differentiation. I first developed an experimental system to analyze promoter activity in primary cultured neuronal cells. Particularly focusing on the transcription regulation of the brain-derived neurotrophic factor (BDNF) gene (Bdnf), I found that the interaction of the cAMP response element-binding protein (CREB) with the CRE sequence is important for the activity-dependent activation of the Bdnf promoter. In addition, this activity-dependent transcriptional regulation occurs in cultured neurons stimulated with excitatory GABAergic inputs, which plays a critical role in promoting the step of neuronal differentiation. Finally, I found that stimulation of the G-protein coupled receptor (GPCR) effectively activates Bdnf promoter IV through selective activation of the calcineurin pathway, irrespective of the type of GPCR if the protein kinase A or C pathway is activated. This induction mechanism appears important to understand intracellular mechanisms evoked via simultaneous neurotransmission of excitatory and modulatory inputs into neurons of the brain.