The Effect of Citalopram on Genome-Wide DNA Methylation of Human Cells

International Journal of Genomics
Riya R KanherkarAntonei B Csoka

Abstract

Commonly used pharmaceutical drugs might alter the epigenetic state of cells, leading to varying degrees of long-term repercussions to human health. To test this hypothesis, we cultured HEK-293 cells in the presence of 50 μM citalopram, a common antidepressant, for 30 days and performed whole-genome DNA methylation analysis using the NimbleGen Human DNA Methylation 3x720K Promoter Plus CpG Island Array. A total of 626 gene promoters, out of a total of 25,437 queried genes on the array (2.46%), showed significant differential methylation (p < 0.01); among these, 272 were hypomethylated and 354 were hypermethylated in treated versus control. Using Ingenuity Pathway Analysis, we found that the chief gene networks and signaling pathways that are differentially regulated include those involved in nervous system development and function and cellular growth and proliferation. Genes implicated in depression, as well as genetic networks involving nucleic acid metabolism, small molecule biochemistry, and cell cycle regulation were significantly modified. Involvement of upstream regulators such as BDNF, FSH, and NFκB was predicted based on differential methylation of their downstream targets. The study validates our hypothesis that pharma...Continue Reading

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Citations

Oct 1, 2020·International Journal of Molecular Sciences·Mikhail V VoroninSergei B Seredenin
Oct 18, 2020·Progress in Neuro-psychopharmacology & Biological Psychiatry·Gordana Nedic ErjavecNela Pivac

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Methods Mentioned

BETA
Chip
histone acetylation

Software Mentioned

R Bioconductor
Ringo
IPA
MEDME
limma
NimbleScan

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