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 gen...
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Published in | Biochemical and biophysical research communications Vol. 394; no. 1; pp. 173 - 177 |
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Main Authors | , , , , , , , , |
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26.03.2010
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Abstract | 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. |
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AbstractList | 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. 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.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. |
Author | Hirai, Akina Chiba, Yusuke Takahashi, Nami Shiraishi, Masahiko Ishimaru, Naoki Tamura, Tomonari Fukuchi, Mamoru Tsuda, Masaaki Tabuchi, Akiko |
Author_xml | – sequence: 1 givenname: Naoki surname: Ishimaru fullname: Ishimaru, Naoki organization: Faculty of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Ootawara, Tochigi 324-8501, Japan – sequence: 2 givenname: Mamoru surname: Fukuchi fullname: Fukuchi, Mamoru organization: Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan – sequence: 3 givenname: Akina surname: Hirai fullname: Hirai, Akina organization: Faculty of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Ootawara, Tochigi 324-8501, Japan – sequence: 4 givenname: Yusuke surname: Chiba fullname: Chiba, Yusuke organization: Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan – sequence: 5 givenname: Tomonari surname: Tamura fullname: Tamura, Tomonari organization: Faculty of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Ootawara, Tochigi 324-8501, Japan – sequence: 6 givenname: Nami surname: Takahashi fullname: Takahashi, Nami organization: Faculty of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Ootawara, Tochigi 324-8501, Japan – sequence: 7 givenname: Akiko surname: Tabuchi fullname: Tabuchi, Akiko organization: Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan – sequence: 8 givenname: Masaaki surname: Tsuda fullname: Tsuda, Masaaki organization: Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan – sequence: 9 givenname: Masahiko surname: Shiraishi fullname: Shiraishi, Masahiko email: mshirais@iuhw.ac.jp organization: Faculty of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Ootawara, Tochigi 324-8501, Japan |
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Keywords | DNA methylation NT-3 Histone acetylation BDNF |
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Snippet | To understand epigenetic regulation of neurotrophins in Neuro-2a mouse neuroblastoma cells, we investigated the alteration of CpG methylation of brain-derived... |
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SubjectTerms | 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 |
Title | Differential epigenetic regulation of BDNF and NT-3 genes by trichostatin A and 5-aza-2′-deoxycytidine in Neuro-2a cells |
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