Nicotine induces chromatin remodelling through decreases in the methyltransferases GLP, G9a, Setdb1 and levels of H3K9me2.
Studies examining the epigenetic effects of nicotine are limited, but indicate that nicotine can promote a transcriptionally permissive chromatin environment by increasing acetylation of histone H3 and H4. To further explore nicotine-induced histone modifications, we measured histone methyltransferase (HMT) mRNA expression as well as total and promoter-specific H3K9me2 levels. Following administration of nicotine, HMT mRNA and H3K9me2 levels were examined in mouse primary cortical neuronal culture and cortex extracted from mice injected intraperitoneally, as well as in human lymphocyte culture. Furthermore, Bdnf/BDNF mRNA levels were examined as an epigenetically regulated read-out of gene expression. There was a significant decrease of the HMT GLP, G9a and Setdb1 mRNA expression in the nicotine-treated tissue examined, with significant decreases seen in both total and promoter-specific H3K9me2 levels. Increasing doses of nicotine resulted in significant decreases in Bdnf/BDNF promoter specific H3K9me2 binding, leading to enhanced Bdnf/BDNF transcription. Taken together, our data suggest that nicotine reduces markers of a restrictive epigenomic state, thereby leading to a more permissive epigenomic environment.
Department of Psychiatry, University of Illinois at Chicago College of Medicine, Chicago, IL, USA.
Kayla A
KA
Chase
Rajiv P
RP
Sharma
D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects*; D047369:Chromatin Immunoprecipitation; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*
D019208:Brain-Derived Neurotrophic Factor; D006657:Histones; D018722:Nicotinic Agonists; D009538:Nicotine; C455847:EHMT1 protein, human; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase; C516239:SETDB1 protein, mouse