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

ABSTRACT: 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.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.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.These results contribute to our understanding of DNA demethylation mechanisms in neurons, and its role in regulating NMDA responsive genes implicated in mental illnesses.

SUBMITTER: Gavin DP

PROVIDER: S-EPMC4520229 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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

Gavin David P DP Kusumo Handojo H Sharma Rajiv P RP Guizzetti Marina M Guidotti Alessandro A Pandey Subhash C SC

Epigenomics 20150101 4

<h4>Aim</h4>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.<h4>Materials & methods</h4>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 promote ...[more]

PMID: 26111030

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