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

Papers of special note have been highlighted as: • of interest

References

• 1. WHO. Suicide. https://www.who.int/news-room/fact-sheets/detail/suicide (18.1.).
  Google Scholar
• 2. WHO. Suicide worldwide in 2019: global health estimates (2021). https://www.who.int/publications/i/item/9789240026643
  Google Scholar
• 3. NIJZ. Svetovni dan preprečevanja samomora (2023). https://nijz.si/mediji/svetovni-dan-preprecevanja-samomora-2023/
  Google Scholar
• 4. Varnik A, Kolves K, Van Der Feltz-Cornelis CM et al. Suicide methods in Europe: a gender-specific analysis of countries participating in the “European Alliance Against Depression”. J. Epidemiol. Community Health 62(6), 545–551 (2008).
  Medline CASGoogle Scholar
• 5. Mirza S, Docherty AR, Bakian A et al. Genetics and epigenetics of self-injurious thoughts and behaviors: systematic review of the suicide literature and methodological considerations. Am. J. Med. Genet B Neuropsychiatr. Genet 189(7–8), 221–246 (2022).
  Medline CASGoogle Scholar
• 6. Edwards AC, Ohlsson H, Moscicki E et al. On the genetic and environmental relationship between suicide attempt and death by suicide. Am. J. Psychiatry 178(11), 1060–1069 (2021).
  MedlineGoogle Scholar
• 7. Cheung S, Woo J, Maes MS, Zai CC. Suicide epigenetics, a review of recent progress. J. Affect. Disord. 265, 423–438 (2020).
  Medline CASGoogle Scholar
• 8. Mann J, Rizk M. A brain-centric model of suicidal behavior. Am. J. Psychiatry 177(10), 902–916 (2020).
  MedlineGoogle Scholar
• 9. Turecki G, Brent DA, Gunnell D et al. Suicide and suicide risk. Nat. Rev. Dis. Primers 5(1), 74 (2019).
  MedlineGoogle Scholar
• 10. Bradvik L. Suicide risk and mental disorders. Int. J. Environ. Res. Public Health 15(9), 2028 (2018).
  MedlineGoogle Scholar
• 11. Zhang J, Li Z. The association between depression and suicide when hopelessness is controlled for. Compr. Psychiatry 54(7), 790–796 (2013).
  MedlineGoogle Scholar
• 12. Ramos-Rosales DF, Vazquez-Alaniz F, Urtiz-Estrada N et al. Epigenetic marks in suicide: a review. Psychiatr. Genet. 31(5), 145–161 (2021). • Great review article explaining about epigenetic marks in suicide.
  Medline CASGoogle Scholar
• 13. Nestler EJ, Pena CJ, Kundakovic M, Mitchell A, Akbarian S. Epigenetic basis of mental illness. Neuroscientist 22(5), 447–463 (2016).
  Medline CASGoogle Scholar
• 14. Turecki G. Epigenetics and suicidal behavior research pathways. Am. J. Prev. Med. 47(2 Suppl. 3), S144–S151 (2014).
  MedlineGoogle Scholar
• 15. Labonte B, Turecki G. The epigenetics of suicide: explaining the biological effects of early life environmental adversity. Arch. Suicide Res. 14(4), 291–310 (2010).
  MedlineGoogle Scholar
• 16. Vaiserman AM, Koliada AK. Early-life adversity and long-term neurobehavioral outcomes: epigenome as a bridge? Hum. Genom. 11(1), 34 (2017).
  MedlineGoogle Scholar
• 17. Mahgoub M, Monteggia LM. Epigenetics and psychiatry. Neurotherapeutics 10(4), 734–741 (2013).
  Medline CASGoogle Scholar
• 18. Roy B, Dwivedi Y. Understanding epigenetic architecture of suicide neurobiology: a critical perspective. Neurosci. Biobehav. Rev. 72, 10–27 (2017).
  MedlineGoogle Scholar
• 19. Sadakierska-Chudy A, Filip M. A comprehensive view of the epigenetic landscape. Part II: histone post-translational modification, nucleosome level, and chromatin regulation by ncRNAs. Neurotox. Res. 27(2), 172–197 (2015).
  Medline CASGoogle Scholar
• 20. Karmodiya K, Krebs AR, Oulad-Abdelghani M, Kimura H, Tora L. H3K9 and H3K14 acetylation co-occur at many gene regulatory elements, while H3K14ac marks a subset of inactive inducible promoters in mouse embryonic stem cells. BMC Genom. 13(424), 1–18 (2012).
  MedlineGoogle Scholar
• 21. Peña CJ, Nestler EJ. Progress in epigenetics of depression. Prog. Mol. Biol. Transl. Sci. 157, 41–66 (2018).
  Medline CASGoogle Scholar
• 22. Narayan PJ, Lill C, Faull R, Curtis MA, Dragunow M. Increased acetyl and total histone levels in post-mortem Alzheimer's disease brain. Neurobiol. Dis. 74, 281–294 (2015).
  Medline CASGoogle Scholar
• 23. Jarmasz JS, Stirton H, Davie JR, Del Bigio MR. DNA methylation and histone post-translational modification stability in post-mortem brain tissue. Clin. Epigenetics 11(1), 5 (2019). • Epigenetic mark, histone post-tranaslational modification is studied for its stability.
  MedlineGoogle Scholar
• 24. Nagy C, Maheu M, Lopez JP et al. Effects of postmortem interval on biomolecule integrity in the brain. J. Neuropathol. Experim. Neurol. 74(5), 459–469 (2015).
  MedlineGoogle Scholar
• 25. Ernst C, Chen ES, Turecki G. Histone methylation and decreased expression of TrkB.T1 in orbital frontal cortex of suicide completers. Mol. Psychiatry 14(9), 830–832 (2009).
  Medline CASGoogle Scholar
• 26. Fiori LM, Gross JA, Turecki G. Effects of histone modifications on increased expression of polyamine biosynthetic genes in suicide. Int. J. Neuropsychopharmacol. 15(8), 1161–1166 (2012).
  Medline CASGoogle Scholar
• 27. Fiori LM, Turecki G. Genetic and epigenetic influences on expression of spermine synthase and spermine oxidase in suicide completers. Int. J. Neuropsychopharmacol. 13(6), 725–736 (2010).
  Medline CASGoogle Scholar
• 28. Fiori LM, Turecki G. Epigenetic regulation of spermidine/spermine N1-acetyltransferase (SAT1) in suicide. J. Psychiatr. Res. 45(9), 1229–1235 (2011).
  MedlineGoogle Scholar
• 29. Nagy C, Torres-Platas SG, Mechawar N, Turecki G. Repression of astrocytic connexins in cortical and subcortical brain regions and prefrontal enrichment of H3K9me3 in depression and suicide. Int. J. Neuropsychopharmacol. 20(1), 50–57 (2017).
  MedlineGoogle Scholar
• 30. Misztak P, Panczyszyn-Trzewik P, Nowak G, Sowa-Kucma M. Epigenetic marks and their relationship with BDNF in the brain of suicide victims. PLOS ONE 15(9), e0239335 (2020). • H3K14ac modification tested on hippocampus of suicide with western blot.
  Medline CASGoogle Scholar
• 31. Lutz PE, Chay MA, Pacis A et al. Non-CG methylation and multiple histone profiles associate child abuse with immune and small GTPase dysregulation. Nat. Commun. 12(1), 1132 (2021).
  Medline CASGoogle Scholar
• 32. Covington HE 3rd, Maze I, Laplant QC et al. Antidepressant actions of histone deacetylase inhibitors. J. Neurosci. 29(37), 11451–11460 (2009). • Article described that administration of HDAC inhibitors reverted H3K14ac level and depressed state.
  Medline CASGoogle Scholar
• 33. Covington HE 3rd, Vialou VF, Laplant Q, Ohnishi YN, Nestler EJ. Hippocampal-dependent antidepressant-like activity of histone deacetylase inhibition. Neurosci. Lett. 493(3), 122–126 (2011).
  Medline CASGoogle Scholar
• 34. Kouter K, Zupanc T, Videtic Paska A. Genome-wide DNA methylation in suicide victims revealing impact on gene expression. J. Affect. Disord. 253, 419–425 (2019).
  Medline CASGoogle Scholar
• 35. Ropret S, Kouter K, Zupanc T, Videtic Paska A. BDNF methylation and mRNA expression in brain and blood of completed suicides in Slovenia. World J. Psychiatry 11(12), 1301–1313 (2021).
  MedlineGoogle Scholar
• 36. Kouter K, Zupanc T, Videtic Paska A. Targeted sequencing approach: comprehensive analysis of DNA methylation and gene expression across blood and brain regions in suicide victims. World J. Biol. Psychiatry 24(1), 12–23 (2023).
  Medline CASGoogle Scholar
• 37. Šalamon Arčan I, Kouter K, Videtič Paska A. Depressive disorder and antidepressants from an epigenetic point of view. World J. Psychiatry 12(9), 1150–1168 (2022).
  MedlineGoogle Scholar
• 38. Jiang H, Lei R, Ding S-W, Zhu S. Skewer: a fast and accurate adapter trimmer for next-generation sequencing paired-end reads. BMC Bioinform. 15, 182 (2014).
  MedlineGoogle Scholar
• 39. Babraham Bioinformatics. FastQC: a quality control tool for high throughput sequence data. http://www.bioinformatics.babraham.ac.uk/projects/fastqc
  Google Scholar
• 40. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25(14), 1754–1760 (2009).
  Medline CASGoogle Scholar
• 41. Li H, Ruan J, Durbin R. Mapping short DNA sequencing reads and calling variants using mapping quality scores. Genome Res. 18(11), 1851–1858 (2008).
  Medline CASGoogle Scholar
• 42. Zhang Y, Liu T, Meyer CA et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9(9), R137 (2008).
  MedlineGoogle Scholar
• 43. Salmon-Divon M, Dvinge H, Tammoja K, Bertone P. PeakAnalyzer: genome-wide annotation of chromatin binding and modification loci. BMC Bioinform. 11, 415 (2010).
  MedlineGoogle Scholar
• 44. Stark R, Brown G. DiffBind: differential binding analysis of ChIP-Seq peak data. https://bioconductor.org/packages/release/bioc/html/DiffBind.html
  Google Scholar
• 45. Thorvaldsdottir H, Robinson JT, Mesirov JP. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform. 14(2), 178–192 (2013).
  Medline CASGoogle Scholar
• 46. Bustin SA, Benes V, Garson JA et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin. Chem. 55(4), 611–622 (2009).
  Medline CASGoogle Scholar
• 47. Vandesompele J, De Preter K, Pattyn F et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Gen. Biol. 3(7), research0034.1 (2002).
  Google Scholar
• 48. Motulsky HJ, Brown RE. Detecting outliers when fitting data with nonlinear regression – a new method based on robust nonlinear regression and the false discovery rate. BMC Bioinform. 7, 123 (2006).
  MedlineGoogle Scholar
• 49. Warde-Farley D, Donaldson SL, Comes O et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 38(Web Server issue), W214–W220 (2010).
  Medline CASGoogle Scholar
• 50. Fang G, Wang W, Paunic V et al. Discovering genetic interactions bridging pathways in genome-wide association studies. Nat. Commun. 10(1), 4274 (2019).
  MedlineGoogle Scholar
• 51. Sokolowski M, Wasserman J, Wasserman D. Gene-level associations in suicide attempter families show overrepresentation of synaptic genes and genes differentially expressed in brain development. Am. J. Med. Genet B Neuropsychiatr. Genet 177(8), 774–784 (2018).
  Medline CASGoogle Scholar
• 52. Kohli MA, Salyakina D, Pfennig A et al. Association of genetic variants in the neurotrophic receptor-encoding gene NTRK2 and a lifetime history of suicide attempts in depressed patients. Arch. Gen. Psychiatry 67(4), 348–359 (2010).
  Medline CASGoogle Scholar
• 53. Docherty AR, Mullins N, Ashley-Koch AE et al. GWAS meta-analysis of suicide attempt: identification of 12 genome-wide significant loci and implication of genetic risks for specific health factors. Am. J. Psychiatry 180(10), 723–738 (2023).
  MedlineGoogle Scholar
• 54. Dóra F, Renner E, Keller D, Palkovits M, Dobolyi A. Transcriptome profiling of the dorsomedial prefrontal cortex in suicide victims. Int. J. Mol. Sci. 23(13), 1–30 (2022).
  Google Scholar
• 55. Monsalve EM, Garcia-Gutierrez MS, Navarrete F, Giner S, Laborda J, Manzanares J. Abnormal expression pattern of Notch receptors, ligands, and downstream effectors in the dorsolateral prefrontal cortex and amygdala of suicidal victims. Mol. Neurobiol. 49(2), 957–965 (2014).
  Medline CASGoogle Scholar
• 56. Arias B, Fabbri C, Serretti A et al. DISC1-TSNAX and DAOA genes in major depression and citalopram efficacy. J. Affect. Disord. 168, 91–97 (2014).
  Medline CASGoogle Scholar
• 57. Pandey GN, Rizavi HS, Bhaumik R, Zhang H. Chemokines gene expression in the prefrontal cortex of depressed suicide victims and normal control subjects. Brain Behav. Immun. 94, 266–273 (2021).
  Medline CASGoogle Scholar
• 58. Cunha RA. Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors. Neurochem. Int. 38(2), 107–125 (2001).
  Medline CASGoogle Scholar
• 59. Pasquini S, Contri C, Merighi S et al. Adenosine receptors in neuropsychiatric disorders: fine regulators of neurotransmission and potential therapeutic targets. Int. J. Mol. Sci. 23(3) (2022).
  Google Scholar
• 60. Leem YH, Jang JH, Park JS, Kim HS. Exercise exerts an anxiolytic effect against repeated restraint stress through 5-HT(2A)-mediated suppression of the adenosine A(2A) receptor in the basolateral amygdala. Psychoneuroendocrinology 108, 182–189 (2019).
  Medline CASGoogle Scholar
• 61. Di Palma M, Sartini S, Lattanzi D et al. Evidence for the existence of A2AR-TrkB heteroreceptor complexes in the dorsal hippocampus of the rat brain: potential implications of A2AR and TrkB interplay upon ageing. Mech. Ageing Dev. 190, 111289 (2020).
  MedlineGoogle Scholar
• 62. Coelho JE, Alves P, Canas PM et al. Overexpression of adenosine A2A receptors in rats: effects on depression, locomotion, and anxiety. Front. Psychiatry 5, 67 (2014).
  MedlineGoogle Scholar
• 63. Crema LM, Pettenuzzo LF, Schlabitz M et al. The effect of unpredictable chronic mild stress on depressive-like behavior and on hippocampal A1 and striatal A2A adenosine receptors. Physiol. Behav. 109, 1–7 (2013). • Research investigating A2A receptor in the depressive state.
  Medline CASGoogle Scholar
• 64. Kaster MP, Machado NJ, Silva HB et al. Caffeine acts through neuronal adenosine A2A receptors to prevent mood and memory dysfunction triggered by chronic stress. Proc. Natl Acad. Sci. USA 112(25), 7833–7838 (2015).
  Medline CASGoogle Scholar
• 65. Bartoli F, Clerici M, Carra G. Purinergic system and suicidal behavior: exploring the link between adenosine A2A receptors and depressive/impulsive features. Mol. Psychiatry 25(3), 512–513 (2020). • In this research, association between impulsivity and A2A receptor was shown.
  Medline CASGoogle Scholar
• 66. Oliveira S, Ardais AP, Bastos CR et al. Impact of genetic variations in ADORA2A gene on depression and symptoms: a cross-sectional population-based study. Purinergic Signal 15(1), 37–44 (2019).
  Medline CASGoogle Scholar
• 67. Kerman IA, Bernard R, Bunney WE et al. Evidence for transcriptional factor dysregulation in the dorsal raphe nucleus of patients with major depressive disorder. Front. Neurosci. 6, 135 (2012).
  Medline CASGoogle Scholar
• 68. Nuzziello N, Craig F, Simone M et al. Integrated analysis of microRNA and mRNA expression profiles: an attempt to disentangle the complex interaction network in attention deficit hyperactivity disorder. Brain Sci. 9(10), 288 (2019).
  Medline CASGoogle Scholar
• 69. Beroun A, Mitra S, Michaluk P, Pijet B, Stefaniuk M, Kaczmarek L. MMPs in learning and memory and neuropsychiatric disorders. Cell. Mol. Life Sci. 76(16), 3207–3228 (2019).
  Medline CASGoogle Scholar
• 70. Dwivedi Y. Brain-derived neurotrophic factor: role in depression and suicide. Neuropsych. Dis. Treatment 5, 433–449 (2009).
  Medline CASGoogle Scholar
• 71. Wang Y, Yuan Q, Xie L. Histone modifications in aging: the underlying mechanisms and implications. Curr. Stem Cell Res. Ther. 13(2), 125–135 (2018).
  Medline CASGoogle Scholar
• 72. Pal S, Tyler JK. Epigenetics and aging. Sci. Advan. 2(7), e1600584 (2016).
  MedlineGoogle Scholar