Sterol Regulatory Element-Binding Protein-2 modulates human brain acyl-CoA hydrolase gene transcription

Mol Cell Biochem. 2005 Jul;275(1-2):199-206. doi: 10.1007/s11010-005-1990-y.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / enzymology*
  • Cell Line, Tumor
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Luciferases / metabolism
  • Neuroblastoma / pathology
  • Palmitoyl-CoA Hydrolase / genetics*
  • Promoter Regions, Genetic
  • Sterol Regulatory Element Binding Protein 2 / metabolism*
  • Transcription, Genetic*
  • Transfection

Substances

  • Sterol Regulatory Element Binding Protein 2
  • Luciferases
  • Palmitoyl-CoA Hydrolase