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


RESULTS
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.


CONCLUSIONS
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.
McGowan
Patrick O
PO
Department of Psychiatry, Douglas Mental Health University Institute, Montreal, Quebec, Canada.
Sasaki
Aya
A
Huang
Tony C T
TC
Unterberger
Alexander
A
Suderman
Matthew
M
Ernst
Carl
C
Meaney
Michael J
MJ
Turecki
Gustavo
G
Szyf
Moshe
M
D001483:Base Sequence; D019175:DNA Methylation; D015870:Gene Expression; D015894:Genome, Human; D005838:Genotype; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011618:Psychotic Disorders / Q000235:genetics*; D012335:RNA, Ribosomal / Q000235:genetics*; D013405:Suicide
D012335:RNA, Ribosomal