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

作者：Ishimaru Naoki; Fukuchi Mamoru; Hirai Akina; Chiba Yusuke; Tamura Tomonari; Takahashi Nami; Tabuchi Akiko; Tsuda Masaaki; Shiraishi Masahiko^*

来源：Biochemical and Biophysical Research Communications, 2010, 394(1): 173-177.

DOI：10.1016/j.bbrc.2010.02.139

• DNA methylation
• Histone acetylation
• BDNF
• NT-3

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.

• 出版日期2010-3-26