Understanding epigenetic architecture of suicide neurobiology: A critical perspective

Abstract

Current understanding of environmental cross-talk with genetic makeup is found to be mediated through an epigenetic interface which is associated with prominent reversible and heritable changes at gene expression level. Recent emergence of epigenetic modulation in shaping the genetic information has become a key regulatory factor in answering the underlying complexities associated with several mental disorders. A comprehensive understanding of the pertinent changes in the epigenetic makeup of suicide phenotype exhibits a characteristic signature with the possibility of using it as a biomarker to help predict the risk factors associated with suicide. Within the scope of this current review, the most sought after epigenetic changes of DNA methylation and histone modification are thoroughly scrutinized to understand their close functional association with the broad spectrum of suicide phenotype.

Keywords: DNA methylation; Epigenetics; Gene expression; Histone modification; Suicide.

Figure 1

Schematic representation showing possible epigenetic regulatory mechanisms proved to impart dynamic alteration in chromatin architecture primarily responsible for reversible switching of transcriptional status within the genomic context of suicidal brain. Covalent attachment of acetyl group or di-methylation on H3K4 residue marks the genome for active transcription with recruitment of RNA PolIII enzyme and associated transcription factors (TFs). Selective tagging of histone tails with tri-methyl groups (e.g. H3K9) mostly restricts the genomic milieu from active transcription. Similar situation prevails when reversible covalent modification of cytosine residues with methyl group transforms the chromatin organization to become repressive. These two fundamental repressive mechanisms (histone modifications and 5′ cytosine methylation) are mostly found to be dynamic in silencing candidate genes in specific brain regions of suicide completers or peripheral tissues like blood mono-nuclear cells of suicide attempters or ideators.