Sterol Regulatory Element-Binding Protein-2 modulates human brain acyl-CoA hydrolase gene transcription.
The brain shows high catalyzing activity during hydrolysis of long-chain acyl-CoAs into fatty acids and CoA-SH. Brain acyl-CoA hydrolase (BACH) is responsible for most of the long-chain acyl-CoA hydrolyzing activity in the brain and is localized exclusively in neurons. We analyzed the human BACH gene promoter, focusing on transcriptional regulation by Sterol Regulatory Element-Binding Protein-2 (SREBP-2), which is a transcription factor that activates genes involved in cholesterol biosynthesis and uptake. When the nuclear form of SREBP-2 gene was transfected into human neuroblastoma cells, transcription of a BACH gene promoter-luciferase reporter gene was activated through a sterol regulatory element (SRE) motif. Moreover, a gel shift assay demonstrated that SREBP-2 specifically bound to the SRE motif. These results suggest that transcription of the BACH gene is activated by SREBP-2. This study also provides insights into BACH function in the interaction between the metabolism of acyl-CoAs and cholesterol in neurons.
Takagi
Mitsuhiro
M
Laboratory of Clinical Biochemistry, Tokyo University of Pharmacy and Life Science, Tokyo, Japan. takagim@ps.toyaku.ac.jp
Suto
Fumitaka
F
Suga
Tetsuya
T
Yamada
Junji
J
D001921:Brain / Q000201:enzymology*; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D010170:Palmitoyl-CoA Hydrolase / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D051782:Sterol Regulatory Element Binding Protein 2; D008156:Luciferases; D010170:Palmitoyl-CoA Hydrolase