PMID- 12114522 OWN - NLM STAT- MEDLINE DCOM- 20021113 LR - 20210206 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 277 IP - 39 DP - 2002 Sep 27 TI - Involvement of an upstream stimulatory factor as well as cAMP-responsive element-binding protein in the activation of brain-derived neurotrophic factor gene promoter I. PG - 35920-31 AB - The use of different brain-derived neurotrophic factor (BDNF) gene promoters results in the differential production of 5'-alternative transcripts, suggesting versatile functions of BDNF in neurons. Among four BDNF promoters I, II, III, and IV (BDNF-PI, -PII, -PIII, and -PIV), BDNF-PI was markedly activated, as well as BDNF-PIII, by Ca(2+) signals evoked via neuronal activity. However, little is known about the mechanisms for the transcriptional activation of BDNF-PI. Using rat cortical neurons in culture, we assigned the promoter sequences responsible for the Ca(2+) signal-mediated activation of BDNF-PI and found that the Ca(2+)-responsive elements were located in two separate (distal and proximal) regions and that the DNA sequences in the proximal region containing cAMP-responsive element (CRE), which is overlapped by the upstream stimulatory factor (USF)-binding element, were largely responsible for the activation of BDNF-PI. CRE-binding protein (CREB) family transcription factors and USF1/USF2 bind to this overlapping site, depending upon their preferred sequences which also control the magnitude of the activation. Overexpression of dominant negative CREB or USF reduced the BDNF-PI activation. These findings support that not only CREB but also USF1/USF2 contributes to Ca(2+) signal-mediated activation of BDNF-PI through the recognition of an overlapping CRE and USF-binding element. FAU - Tabuchi, Akiko AU - Tabuchi A AD - Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama, Japan. FAU - Sakaya, Hidemichi AU - Sakaya H FAU - Kisukeda, Tomochika AU - Kisukeda T FAU - Fushiki, Hiroshi AU - Fushiki H FAU - Tsuda, Masaaki AU - Tsuda M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20020711 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 660YQ98I10 (Potassium Chloride) RN - 9007-49-2 (DNA) RN - E0399OZS9N (Cyclic AMP) RN - EC 1.13.12.- (Luciferases) RN - EC 3.2.1.23 (beta-Galactosidase) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Base Sequence MH - Binding Sites MH - Brain-Derived Neurotrophic Factor/*genetics/*metabolism MH - Calcium/metabolism MH - Cell Nucleus/metabolism MH - Cells, Cultured MH - Cyclic AMP/metabolism MH - Cyclic AMP Response Element-Binding Protein/*chemistry/*metabolism MH - DNA/metabolism MH - Enzyme Activation MH - Exons MH - Gene Deletion MH - Genes, Dominant MH - Genes, Reporter MH - Genetic Vectors MH - Luciferases/metabolism MH - Male MH - Molecular Sequence Data MH - Mutation MH - Neurons/metabolism MH - Plasmids/metabolism MH - Potassium Chloride/pharmacology MH - *Promoter Regions, Genetic MH - Protein Binding MH - Rats MH - Rats, Sprague-Dawley MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transcription, Genetic MH - Transcriptional Activation MH - Transfection MH - beta-Galactosidase/metabolism EDAT- 2002/07/13 10:00 MHDA- 2002/11/26 04:00 CRDT- 2002/07/13 10:00 PHST- 2002/07/13 10:00 [pubmed] PHST- 2002/11/26 04:00 [medline] PHST- 2002/07/13 10:00 [entrez] AID - S0021-9258(18)36555-4 [pii] AID - 10.1074/jbc.M204784200 [doi] PST - ppublish SO - J Biol Chem. 2002 Sep 27;277(39):35920-31. doi: 10.1074/jbc.M204784200. Epub 2002 Jul 11.