Differential epigenetic regulation of BDNF and NT-3 genes by trichostatin A and 5-aza-2′-deoxycytidine in Neuro-2a cells

• Published in: Biochemical and biophysical research communications Vol. 394; no. 1; pp. 173 - 177
• Main Authors: Ishimaru, Naoki, Fukuchi, Mamoru, Hirai, Akina, Chiba, Yusuke, Tamura, Tomonari, Takahashi, Nami, Tabuchi, Akiko, Tsuda, Masaaki, Shiraishi, Masahiko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.03.2010
• Subjects: Acetylation; Animals; Azacitidine - analogs & derivatives; Azacitidine - pharmacology; BDNF; Brain-Derived Neurotrophic Factor - genetics; Cell Line, Tumor; Chromatin Immunoprecipitation; CpG Islands; DNA Methylation; DNA Modification Methylases - antagonists & inhibitors; Epigenesis, Genetic; Exons - genetics; Histone acetylation; Histones - metabolism; Hydroxamic Acids - pharmacology; Mice; Nerve Growth Factors - genetics; Neurons - drug effects; Neurons - metabolism; NT-3; Promoter Regions, Genetic; DNA methylation; NT-3; Histone acetylation; BDNF
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2010.02.139

To understand epigenetic regulation of neurotrophins in Neuro-2a mouse neuroblastoma cells, we investigated the alteration of CpG methylation of brain-derived neurotrophic factor (BDNF) promoter I and neurotrophin-3 (NT-3) promoter IB and that of histone modification in Neuro-2a cells. Bisulfite genomic sequencing showed that the CpG sites of BDNF promoter I were methylated in non-treated Neuro-2a cells and demethylated following 5-aza-2′-deoxycytidine (5-aza-dC) treatment. In contrast, methylation status of the NT-3 promoter IB did not change by 5-aza-dC treatment in Neuro-2a cells. Furthermore, we demonstrated that BDNF exon I–IX mRNA was induced by trichostatin A (TSA) treatment. However, NT-3 exon IB–II mRNA was not induced by TSA treatment. Chromatin immunoprecipitation assays showed that the levels of acetylated histones H3 and H4 on BDNF promoter I were increased by TSA. These results demonstrate that DNA methylation and/or histone modification regulate BDNF gene expression, but do not regulate NT-3 gene expression in Neuro-2a cells.