NDLI: Identification and analysis of the promoter region of the human DHCR24 gene: involvement of DNA methylation and histone acetylation

Content Provider	Springer Nature Link
Author	Drzewinska, Joanna Walczak Drzewiecka, Aurelia Ratajewski, Marcin
Copyright Year	2010
Abstract	Mutations in the DHCR24 gene, which encodes the cholesterol biosynthesis enzyme 3ß-hydroxysterol-∆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.
Starting Page	1091
Ending Page	1101
Page Count	11
File Format	PDF
ISSN	03014851
Journal	Molecular Biology Reports
Volume Number	38
Issue Number	2
e-ISSN	15734978
Language	English
Publisher	Springer Netherlands
Publisher Date	2010-06-22
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	DHCR24 Gene promoter DNA methylation Histone acetylation Tissue specificity Gene regulation Animal Biochemistry Animal Anatomy / Morphology / Histology
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine Molecular Biology

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