Epigenetics and suicide: investigating altered H3K14ac unveiled differential expression in ADORA2A, B4GALT2 and MMP14

Abstract

Background: Environmental factors make an important contribution to suicide. Histone tails are prone to different modifications, leading to changes of chromatin (de)condensation and consequently gene expression. Materials & methods: Level of H3K14ac was studied with chromatin immunoprecipitation followed by high-throughput DNA sequencing. Genes were further validated with RT-qPCR; using hippocampal tissue. Results: We showed lowered H3K14ac levels in individuals who died by suicide. The genes ADORA2A, B4GALT2 and MMP14 showed differential expression in individuals who died by suicide. Identified genetic and protein interactions among genes show interactions with suicide-related genes. Conclusion: Further investigations of histone modifications in association with DNA methylation and miRNA are needed to expand our knowledge of the genes that could significantly contribute to suicide.

Summary points

• Epigenetics importantly contributes to the development of mental disorders and suicidality.

• Post-translational modifications of the histone tail importantly contribute to the opening or closing of the chromatin.

• Hippocampus of 20 suicides and 20 control subjects were included in the study.

• H3K14ac level was investigated in hippocampus of suicides, compared with the controls.

• Chromatin immunoprecipitation followed by high-throughput DNA sequencing determined the level of H3K14ac.

• Genes ADORA2A, B4GALT2 and MMP14 were differentially expressed in suicides compared with controls.

• Lowered H3K14ac level was associated with lowered gene expressions of differentially expressed genes.

• ADORA2A has been studied in several neuropsychiatric pathologies.

• ADORA2A and B4GALT2 are in interaction with NTRK2 gene.

Keywords: :

• ADORA2A
• B4GALT2
• ChIP-seq
• chromatin immunoprecipitation
• epigenetics
• H3K14ac
• MMP14
• sequencing
• suicide

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/epi-2023-0351

Financial disclosure

This work was funded by the Slovenian Research Agency: grants for Young Researcher, and Research Programme P1-0390. Funding source was not involved in research and/or preparation of this article.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The study was approved by the National Medical Ethics Committee of the Republic of Slovenia (0120-520/2019/4).

Acknowledgments

The authors would like to thank JM Hancock for critical appraisal and scientific English editing of the manuscript.

Additional information

Funding

This work was funded by the Slovenian Research Agency: grants for Young Researcher, and Research Programme P1-0390. Funding source was not involved in research and/or preparation of this article.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.