Gadd45b and N-methyl-d-aspartate induced DNA demethylation in postmitotic neurons

David P. Gavin, Handojo Kusumo, Rajiv P. Sharma, Marina Guizzetti, Alessandro Guidotti, Subhash C. Pandey

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)567-579
Number of pages13
JournalEpigenomics
Volume7
Issue number4
DOIs
StatePublished - Jun 1 2015

Keywords

  • CpG
  • alcoholism
  • epigenetic
  • histone
  • schizophrenia

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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    Gavin, D. P., Kusumo, H., Sharma, R. P., Guizzetti, M., Guidotti, A., & Pandey, S. C. (2015). Gadd45b and N-methyl-d-aspartate induced DNA demethylation in postmitotic neurons. Epigenomics, 7(4), 567-579. https://doi.org/10.2217/epi.15.12