期刊
EPIGENOMICS
卷 7, 期 4, 页码 567-579出版社
FUTURE MEDICINE LTD
DOI: 10.2217/EPI.15.12
关键词
alcoholism; CpG; epigenetic; histone; schizophrenia
资金
- Department of Veterans Affairs Career Development Award [CDA-2, IK2BX001650]
- Research Career Scientist award
- VHA [I01BX001819]
- NIH/National Institute on Alcohol Abuse and Alcoholism Grants (NIAAA) [AA-010005, AA021876]
- NARSAD Young Investigator Award
Aim: In nondividing neurons examine the role of Gadd45b in active 5-methylcytosine (5MC) and 5-hydroxymethylcytosine (5HMC) removal at a gene promoter highly implicated in mental illnesses and cognition, Bdnf. Materials & methods: Mouse primary cortical neuronal cultures with and without Gadd45b siRNA transfection were treated with N-methyl-D-aspartate (NMDA). Expression changes of genes reportedly involved in DNA demethylation, Bdnf mRNA and protein and 5MC and 5HMC at Bdnf promoters were measured. Results: Gadd45b siRNA transfection in neurons abolishes the NMDA-induced increase in Bdnf IXa mRNA and reductions in 5MC and 5HMC at the Bdnf IXa promoter. Conclusion: These results contribute to our understanding of DNA demethylation mechanisms in neurons, and its role in regulating NMDA responsive genes implicated in mental illnesses.
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