Effects of histone modifications on increased expression of polyamine biosynthetic genes in suicide.
Altered polyamine metabolism has been consistently observed as underlying the suicide process. We recently performed a global analysis of polyamine gene expression across the brains of suicide completers, and identified up-regulation of four genes, arginase II (ARG2), S-adenosylmethionine decarboxylase (AMD1), and antizymes 1 and 2 (OAZ1 and OAZ2), which play essential roles in polyamine biosynthesis. To determine if a shared epigenetic mechanism is involved in their overexpression in the prefrontal cortex, we measured promoter levels of tri-methyl modified histone-3-lysine-4 (H3K4me3), a marker of open chromatin, and assessed its association with suicide and gene expression. We identified increased H3K4me3 in the promoter region of OAZ1 in suicide, and found that H3K4me3 was correlated with the expression of OAZ1 and ARG2. Overall, our findings indicate that the H3K4me3 modification plays an important role in the regulation of polyamine biosynthesis, and that this mechanism may be involved in the neurobiology of suicide.
McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Verdun, Quebec, Canada.
Laura M
LM
Fiori
Jeffrey A
JA
Gross
Gustavo
G
Turecki
D012437:Adenosylmethionine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011073:Polyamines / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D011506:Proteins; D013405:Suicide; D015854:Up-Regulation / Q000502:physiology*
D004268:DNA-Binding Proteins; D006657:Histones; D011073:Polyamines; D011506:Proteins; C031017:ornithine decarboxylase antizyme; C477631:ARG2 protein, human; D001119:Arginase; D012437:Adenosylmethionine Decarboxylase