Journal
MOLECULAR BIOLOGY REPORTS
Volume 38, Issue 2, Pages 1091-1101Publisher
SPRINGER
DOI: 10.1007/s11033-010-0206-z
Keywords
DHCR24; Gene promoter; DNA methylation; Histone acetylation; Tissue specificity; Gene regulation
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Funding
- Polish Ministry of Science and Higher Education [N N301 164335]
- Institute of Medical Biology
- University of Lodz
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Mutations in the DHCR24 gene, which encodes the cholesterol biosynthesis enzyme 3-hydroxysterol-a dagger 24 reductase, result in an autosomal recessive disease called desmosterolosis. Further, reduced expression of DHCR24 is found in the temporal cortex of Alzheimer's disease patients. This suggests that variability in the regulatory regions of DHCR24 may contribute to the development of this neurodegenerative disease. In this work, we functionally characterised the proximal fragment of the human DHCR24 gene, for the first time. We show that the transcription of DHCR24 is initiated from a single CpG-rich promoter that is regulated by DNA methylation in some cell types. An activator sequence was also uncovered in the -1203/-665 bp region by reporter gene assays. Furthermore, sodium butyrate (a well-known HDAC inhibitor) increased DHCR24 expression in SH-SY5Y cells by recruiting acetylated core histones H3 and H4 to the enhancer region, as demonstrated by transient transfection and chromatin immunoprecipitation assays. Understanding the regulation of the DHCR24 gene may lead to alternative therapeutic strategies in at least some Alzheimer's patients.
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