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. Author manuscript; available in PMC: 2015 Oct 9.
Published in final edited form as: J Mol Biol. 2014 Apr 5;426(20):3389–3412. doi: 10.1016/j.jmb.2014.03.016

Figure 3. Regulation of GABAA receptor subunit gene expression in NAc through crosstalk between histone acetylation and repressive methylation.

Figure 3

Repeated cocaine targets HDAC1 to the G9a/GLP (G9a-like protein) promoters, leading to decreased G9a/GLP gene expression and decreased binding of these histone methyltransferases (HMTs) at the promoters of certain GABAA receptor subunit genes. The resulting decreased repressive histone methylation (reduced H3K9me2) allows for increased transcription of the GABAA receptor subunits and increased inhibitory tone in the NAc. Chronic cocaine plus chronic intra-NAc infusion of MS275, by inhibiting HDAC1, promotes excessive histone acetylation at several genes, including G9a/GLP, and leads to the induction of G9a/GLP gene expression. These HMTs then catalyze increased H3K9me2 at GABAA receptor subunit gene promoters to block cocaine-induced transcriptional activation of the GABAA subunits and increased inhibitory tone. From Ref 130, with permission.