Differential epigenetic regulation of BDNF and NT-3 genes by trichostatin A and 5-aza-2'-deoxycytidine in Neuro-2a cells.
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.
Ishimaru
Naoki
N
Faculty of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Ootawara, Tochigi 324-8501, Japan.
Fukuchi
Mamoru
M
Hirai
Akina
A
Chiba
Yusuke
Y
Tamura
Tomonari
T
Takahashi
Nami
N
Tabuchi
Akiko
A
Tsuda
Masaaki
M
Shiraishi
Masahiko
M
D000107:Acetylation; D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005091:Exons / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D009414:Nerve Growth Factors / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic
D019208:Brain-Derived Neurotrophic Factor; D006657:Histones; D006877:Hydroxamic Acids; D009414:Nerve Growth Factors; C518911:neurotropin 3, mouse; C012589:trichostatin A; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine