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.
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.
Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama, Japan.
Akiko
A
Tabuchi
Hidemichi
H
Sakaya
Tomochika
T
Kisukeda
Hiroshi
H
Fushiki
Masaaki
M
Tsuda
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry* / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation; D005091:Exons; D017353:Gene Deletion; D005799:Genes, Dominant; D017930:Genes, Reporter; D005822:Genetic Vectors; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D011189:Potassium Chloride; D004247:DNA; D000242:Cyclic AMP; D008156:Luciferases; D001616:beta-Galactosidase; D002118:Calcium