Work

Gadd45b and N -Methyl- d -Aspartate Induced DNA Demethylation in Postmitotic Neurons

Year: 2015

Type: article

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.

Source: Epigenomics

DOI: 10.2217/epi.15.12

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

Institutions: University of Illinois Chicago, Jesse Brown VA Medical Center, Oregon Health & Science University, VA Portland Health Care System

Language: English

Topic: Epigenetics and DNA Methylation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: U.S. Department of Veterans Affairs, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Institute of Mental Health