Gadd45b and N-methyl-d-aspartate induced DNA demethylation in postmitotic neurons. (June 2015)

• Record Type: Journal Article
• Authors: Gavin, David P; Kusumo, Handojo; Sharma, Rajiv P; Guizzetti, Marina; Guidotti, Alessandro; Pandey, Subhash C
• Is Part Of: Epigenomics. Volume 7:Number 4(2015)
• Page Start: 567
• Page End: 579
• Publication Date: 2015-06
• Subjects: alcoholism -- CpG -- epigenetic -- histone -- schizophrenia; Epigenesis -- Periodicals; Genomics -- Periodicals; Chromatin -- Periodicals; DNA -- Periodicals; 572.87
• DOI: 10.2217/epi.15.12
• Languages: English
• ISSNs: 1750-1911

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.