DNA methylation landscape of the genes regulating D-serine and D-aspartate metabolism in post-mortem brain from controls and subjects with schizophrenia

Simona Keller, Daniela Punzo, Mariella Cuomo, Ornella Affinito, Lorena Coretti, Silvia Sacchi, Ermanno Florio, Francesca Lembo, Massimo Carella, Massimiliano Copetti, Sergio Cocozza, Darrick T. Balu, Francesco Errico, Alessandro Usiello, Lorenzo Chiariotti

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The spatio-temporal regulation of genes involved in the synthesis and degradation of D-serine and D-aspartate such as serine racemase (SR), D-amino acid oxidase (DAO), G72 and D-aspartate oxidase (DDO), play pivotal roles in determining the correct levels of these D-amino acids in the human brain. Here we provide a comprehensive analysis of mRNA expression and DNA methylation status of these genes in post-mortem samples from hippocampus, dorsolateral prefrontal cortex, and cerebellum from patients with schizophrenia and non-psychiatric controls. DNA methylation analysis was performed at an ultradeep level, measuring individual epialleles frequency by single molecule approach. Differential CpG methylation and expression was detected across different brain regions, although no significant correlations were found with diagnosis. G72 showed the highest CpG and non-CpG methylation degree, which may explain the repression of G72 transcription in the brain regions considered here. Conversely, in line with the sustained SR mRNA expression in the analyzed areas, very low methylation levels were detected at this gene's regulatory regions. Furthermore, for DAO and DDO, our single-molecule methylation approach demonstrated that analysis of epiallele distribution was able to detect differences in DNA methylation representing area-specific methylation signatures, which are likely not detectable with targeted or genome-wide classic methylation analyses.

Original languageEnglish
Article number28332
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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D-Aspartic Acid
DNA Methylation
Serine
Methylation
Schizophrenia
Brain
D-Amino-Acid Oxidase
Genes
D-Aspartate Oxidase
Messenger RNA
Nucleic Acid Regulatory Sequences
Prefrontal Cortex
Cerebellum
Hippocampus
Genome
Amino Acids

ASJC Scopus subject areas

  • General

Cite this

DNA methylation landscape of the genes regulating D-serine and D-aspartate metabolism in post-mortem brain from controls and subjects with schizophrenia. / Keller, Simona; Punzo, Daniela; Cuomo, Mariella; Affinito, Ornella; Coretti, Lorena; Sacchi, Silvia; Florio, Ermanno; Lembo, Francesca; Carella, Massimo; Copetti, Massimiliano; Cocozza, Sergio; Balu, Darrick T.; Errico, Francesco; Usiello, Alessandro; Chiariotti, Lorenzo.

In: Scientific Reports, Vol. 8, No. 1, 28332, 01.12.2018.

Research output: Contribution to journalArticle

Keller, S, Punzo, D, Cuomo, M, Affinito, O, Coretti, L, Sacchi, S, Florio, E, Lembo, F, Carella, M, Copetti, M, Cocozza, S, Balu, DT, Errico, F, Usiello, A & Chiariotti, L 2018, 'DNA methylation landscape of the genes regulating D-serine and D-aspartate metabolism in post-mortem brain from controls and subjects with schizophrenia', Scientific Reports, vol. 8, no. 1, 28332. https://doi.org/10.1038/s41598-018-28332-x
Keller, Simona ; Punzo, Daniela ; Cuomo, Mariella ; Affinito, Ornella ; Coretti, Lorena ; Sacchi, Silvia ; Florio, Ermanno ; Lembo, Francesca ; Carella, Massimo ; Copetti, Massimiliano ; Cocozza, Sergio ; Balu, Darrick T. ; Errico, Francesco ; Usiello, Alessandro ; Chiariotti, Lorenzo. / DNA methylation landscape of the genes regulating D-serine and D-aspartate metabolism in post-mortem brain from controls and subjects with schizophrenia. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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