Nicotine induces chromatin remodelling through decreases in the methyltransferases GLP, G9a, Setdb1 and levels of H3K9me2
journal contributionposted on 10.06.2014 by Kayla A. Chase, Rajiv P. Sharma
Any type of content formally published in an academic journal, usually following a peer-review process.
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.