Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain

• Published in: PloS one Vol. 3; no. 5; p. e2085
• Main Authors: McGowan, Patrick O, Sasaki, Aya, Huang, Tony C T, Unterberger, Alexander, Suderman, Matthew, Ernst, Carl, Meaney, Michael J, Turecki, Gustavo, Szyf, Moshe
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.05.2008; Public Library of Science (PLoS)
• Subjects: Aberration; Abuse; Alzheimer's disease; Base Sequence; Behavior disorders; Bisulfite; Brain; Cerebellum; Child abuse & neglect; Childhood; Children; Cognitive ability; Deoxyribonucleic acid; DNA; DNA Methylation; Emotional disorders; Epigenetic inheritance; Epigenetics; Gene Expression; Gene mapping; Genes; Genetics; Genetics and Genomics/Epigenetics; Genetics and Genomics/Medical Genetics; Genome, Human; Genomes; Genomics; Genotype; Hippocampus; Hippocampus - physiopathology; Humans; Impulsivity; Machinery; Mental health; Mental Health/Neuropsychiatric Disorders; Methylation; Molecular Biology/DNA Methylation; Molecular Sequence Data; Neurology; Neuroscience; Neurosurgery; Pathology/Pathophysiology; Pediatrics and Child Health/Child Abuse; Personality disorders; Pharmacology; Physiology/Genomics; Polymerase Chain Reaction; Promoter Regions, Genetic; Protein biosynthesis; Protein synthesis; Psychiatry; Psychobiology; Psychotic Disorders - genetics; Ribonucleic acid; Ribosomal RNA; RNA; RNA polymerase; RNA, Ribosomal - genetics; rRNA; Sodium; Studies; Suicide; Suicide genes; Suicides & suicide attempts; Sulfites; Transcription (Genetics); Canada; Montreal Quebec Canada; Quebec Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0002085

Alterations in gene expression in the suicide brain have been reported and for several genes DNA methylation as an epigenetic regulator is thought to play a role. rRNA genes, that encode ribosomal RNA, are the backbone of the protein synthesis machinery and levels of rRNA gene promoter methylation determine rRNA transcription. We test here by sodium bisulfite mapping of the rRNA promoter and quantitative real-time PCR of rRNA expression the hypothesis that epigenetic differences in critical loci in the brain are involved in the pathophysiology of suicide. Suicide subjects in this study were selected for a history of early childhood neglect/abuse, which is associated with decreased hippocampal volume and cognitive impairments. rRNA was significantly hypermethylated throughout the promoter and 5' regulatory region in the brain of suicide subjects, consistent with reduced rRNA expression in the hippocampus. This difference in rRNA methylation was not evident in the cerebellum and occurred in the absence of genome-wide changes in methylation, as assessed by nearest neighbor. This is the first study to show aberrant regulation of the protein synthesis machinery in the suicide brain. The data implicate the epigenetic modulation of rRNA in the pathophysiology of suicide.