H3K9me2: Perbedaan antara revisi

[[Berkas:Methylation-lysine.PNG|jmpl|Kata "'''dimetilasi'''" menunjukkan adanya tambahan '''dua gugus metil''' pada lisina seperti pada '''H3K9me2'''.]]

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ΔFosB serves as one of the master control proteins governing this structural plasticity.&nbsp;... ΔFosB also represses G9a expression, leading to reduced repressive histone methylation at the cdk5 gene. The net result is gene activation and increased CDK5 expression.&nbsp;... In contrast, ΔFosB binds to the c-fos gene and recruits several co-repressors, including HDAC1 (histone deacetylase 1) and SIRT 1 (sirtuin 1).&nbsp;... The net result is c-fos gene repression.&nbsp;... G9a and ΔFosB share many of the same target genes.&nbsp;... Histone methylation is directly regulated by drugs of abuse as well: global levels of histone 3 lysine 9 dimethylation (H3K9me2) are reduced in the NAc after chronic cocaine37 and a genome-wide screen revealed alterations in H3K9me2 binding on the promoters of numerous genes in this brain region32; both increases and decreases were observed, indicating again that epigenetic modifications at individual genes often defy global changes. The global decrease in H3K9me2 in the NAc is likely mediated by cocaine-induced downregulation of two HMTs, G9a and G9a-like protein (GLP), which catalyze H3K9me2³⁷. These adaptations mediate enhanced responsiveness to cocaine, as selective knockout or pharmacological inhibition of G9a in the NAc promotes cocaine-induced behaviors, whereas G9a overexpression has the opposite effect. G9a likewise mediates the ability of cocaine to increase the spine density of NAc MSNs³⁷ (Box 2). Interestingly, there is a functional feedback loop between G9a and ΔFosB: ΔFosB seems to be responsible for cocaine-induced suppression of G9a, and G9a binds to and represses the fosb promoter, such that G9a downregulation may promote the accumulation of ΔFosB observed after chronic cocaine³⁷. In addition, G9a and ΔFosB share many of the same target genes.&nbsp;... The mechanisms underlying such gene desensitization and priming remain incompletely understood; our hypothesis is that epigenetic mechanisms are crucial (Figure 3B). An subset of primed genes show reduced binding of G9a and H3K9me2 at their promoters in the NAc, suggesting the involvement of this epigenetic mark³⁷. Desensitization of the c-fos gene in the NAc, discussed above and depicted in Figure 4, involves stable increases in the binding of ΔFosB, G9a, and related co-repressors, which—although not affecting steady-state levels of c-Fos mRNA—dramatically repress its inducibility to subsequent drug exposure⁹¹.-->|vauthors=Robison AJ, Nestler EJ}}