Brain Gene Expression-DNA Methylation Correlation in Suicide Completers: Preliminary Results



Título del documento: Brain Gene Expression-DNA Methylation Correlation in Suicide Completers: Preliminary Results
Revista: Revista de investigación clínica
Base de datos: PERIÓDICA
Número de sistema: 000453203
ISSN: 0034-8376
Autores: 1
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Instituciones: 1Instituto Nacional de Medicina Genómica, Laboratorio de Genómica de Enfermedades Psiquiátricas y Neurodegenerativas, Ciudad de México. México
2Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Departamento de Genética, Ciudad de México. México
3University of Texas, Health Science Center at Houston, Houston, Texas. Estados Unidos de América
4Instituto de Ciencias Forenses, Ciudad de México. México
5Benemérita Universidad Autónoma de Puebla, Instituto de Fisiología, Puebla. México
Año:
Periodo: Sep-Oct
Volumen: 72
Número: 5
Paginación: 283-292
País: México
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Experimental, aplicado
Resumen en inglés Background: Gene 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. Objective: The objective of the study was to identify genes whose expression levels are correlated with DNA methylation in the prefrontal cortex of suicides. Methods: Postmortem 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. Results: We 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 non-suicide 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. Conclusions: The 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
Disciplinas: Medicina
Palabras clave: Neurología,
Psiquiatría,
Genética,
Suicidio,
Metilación del ADN,
Expresión génica,
Corteza cerebral,
Microarreglos genéticos,
Factores de transcripción,
Neurodesarrollo
Keyword: Neurology,
Psychiatry,
Genetics,
Suicide,
DNA methylation,
Gene expression,
Cerebral cortex,
Genetic microarrays,
Transcription factors,
Neurodevelopment
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