Transcriptional regulation of acetoacetyl-CoA synthetase by Sp1 in neuroblastoma cells
- Department of Health Chemistry, Hoshi University, Shinagawa, Tokyo, 142-8501 (Japan)
Highlights: • The core promoter of AACS is located in a region with 110 bps upstream from the TSS. • Sp1 interacts with an Sp1 binding site in the promoter region of AACS. • Overexpression of Sp1 upregulates AACS mRNA levels. • Knockdown of AACS results in downregulation of HDAC9. Acetoacetyl-CoA synthetase (AACS) is the enzyme responsible for cholesterol and fatty acid synthesis in the cytosol. We have previously shown that AACS has an important role in normal neuronal development and that knockdown of SREBP-2, which orchestrates cholesterol synthesis, resulted in the downregulation of AACS mRNA levels. In this study, we investigated the transcriptional mechanism of AACS in Neuro-2a, neuroblastoma cells. Luciferase assay showed that the minimal core promoter of the mouse AACS gene is located in a region with 110 bps upstream from the transcription start site. Mutagenesis studies showed that the Sp1 binding site was crucial for AACS promoter activity. ChIP assay and DNA affinity precipitation assay showed that Sp1 binds to the Sp1 binding site on the promoter region of AACS. Moreover, overexpression of Sp1 increased AACS mRNA levels. Knockdown of AACS resulted in a decrease in histone deacetylase 9, associated with gene silencing. These results suggest that Sp1 regulates gene expression of AACS in Neuro-2a cells and ketone body utilization affects the balance of histone acetylation.
- OSTI ID:
- 23100617
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 495, Issue 1; Other Information: Copyright (c) 2017 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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