• Brenda Cabrera-Mendoza, José J Martínez-Magaña, Alma D Genis-Mendoza, Nancy Monroy-Jaramillo, Consuelo Walss-Bass, Gabriel R Fries, Fernando García-Dolores, Mauro López-Armenta, Gonzalo Flores, Rubén A Vázquez-Roque, and Humberto Nicolini.
• Genomics of Psychiatric and Neurodegenerative Diseases Laboratory, Instituto Nacional de Medicina Genómica, SSA, Mexico City, Mexico; Combined Studies Program in Medicine MD/PhD, Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico.
• Rev Invest Clin. 2020 May 7; 72 (5): 283-292.

BackgroundGene expression alterations have been implicated in suicide pathology. However, the study of the regulatory effect of DNA methylation on gene expression in the suicidal brain has been restricted to candidate genes.ObjectiveThe objective of the study was to identify genes whose expression levels are correlated with DNA methylation in the prefrontal cortex of suicides.MethodsPostmortem prefrontal cortex samples from 21 suicides and six non-suicides were collected. Transcriptomic and DNA methylation profiles were evaluated with microarrays; cis correlations between gene expression and CpG methylation were screened. We then analyzed the presence of transcription factor (TF) binding sites (TFBS) at CpG sites correlated with gene expression. Gene expression of TFs involved in neurodevelopmental binding to predicted TFBS was determined in the BrainSpan database.ResultsWe identified 22 CpG sites whose methylation levels correlated with gene expression in the prefrontal cortex of suicides. Genes annotated to identified CpG sites were involved in neurodevelopment (BBS4, NKX6-2, AXL, CTNND1, and MBP) and polyamine metabolism (polyamine oxidase [PAOX]). Such correlations were not detected in the nonsuicide group. Nine TFs (USF1, TBP, SF1, NRF1, RFX1, SP3, PKNOX1, MAZ, and POU3F2) showed differential expression in pre- and post-natal developmental periods, according to BrainSpan database.ConclusionsThe integration of different omic technologies provided novel candidates for the investigation of genes whose expression is altered in the suicidal brain and their potential regulatory mechanisms.

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