PMID- 25832840 OWN - NLM STAT- MEDLINE DCOM- 20160621 LR - 20150402 IS - 1347-5231 (Electronic) IS - 0031-6903 (Linking) VI - 135 IP - 4 DP - 2015 TI - [Gene regulation involved in the formation of long-term memory]. PG - 597-617 LID - 10.1248/yakushi.14-00241 [doi] AB - 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. FAU - Tsuda, Masaaki AU - Tsuda M AD - Laboratory of Molecular Neurobiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama. LA - jpn PT - English Abstract PT - Journal Article PT - Review PL - Japan TA - Yakugaku Zasshi JT - Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan JID - 0413613 SB - IM MH - Animals MH - Brain MH - *Gene Expression Regulation MH - Genomics MH - Humans MH - *Memory, Long-Term MH - Promoter Regions, Genetic MH - Transcription, Genetic EDAT- 2015/04/04 06:00 MHDA- 2016/06/22 06:00 CRDT- 2015/04/03 06:00 PHST- 2015/04/03 06:00 [entrez] PHST- 2015/04/04 06:00 [pubmed] PHST- 2016/06/22 06:00 [medline] AID - 10.1248/yakushi.14-00241 [doi] PST - ppublish SO - Yakugaku Zasshi. 2015;135(4):597-617. doi: 10.1248/yakushi.14-00241.