Drug-Induced Epigenetic Changes Produce Drug Tolerance
Figure 6
Induction of CREB Dominant-Negative Transgene Blocks Acetylation Changes Produced by Benzyl Alcohol Sedation
The histone H4 acetylation profile across the slo control region was assayed by ChromIP and real-time PCR 4 h after BA sedation. Fold change is the ratio of H4 acetylation of sedated animals to mock-sedated control animals.
(A) Without heat induction (NoHS; blue bars) of the dominant-negative CREB transgene (hs-dCREB2b), there are significant changes in H4 acetylation at cre1, 55b, and cre2. These changes in H4 acetylation were blocked by heat-pulse induction of hs-dCREB2b (HS; red bars) 1 h before BA sedation.
(B) BA sedation of the Canton S (CS) stock (wild-type, nontransgenic) produces the same acetylation profile regardless of whether the stock had also been heat treated (HS; red bars) or not heat treated (NoHS; blue bars). The graph depicts data from four independent experiments (mean ± SEM). Statistical significance refers to the difference between the NoHS and HS treatments, and was determined by two-way ANOVA (n = 4; a single asterisk [*] indicates p < 0.05, and double asterisks [**] indicate p < 0.01).