Epigenetic regulation of slo

 
We have shown that sedation with benzyl alcohol or ethanol induces slo gene expression. But how does the gene sense sedation? In Yan et al 2007 and 2009 we show that sedation activates CREB signaling and that this causes a change in histone acetylation levels across the slo promoter region leading to gene induction. Blocking CREB blocks histone acetylation, gene induction and behavioral tolerance. Histone acetylation is an epigenetic modification that usually causes increased gene expression. Recently, we have observed that sedation induces other epigenetic marks on the slo promoter region. These may enable the gene to “remember” the previous sedation. Perhaps, this leads to changed response to future drug insults. Once we know where an epigenetic mark occurs we use homologous recombination delete the underlying site and see if the mutation alters the response of slo to drugs. Wang, Y et al. (2009) CREB regulation of BK channel gene expression underlies rapid drug tolerance. Genes Brain Behav, 8:369–376. Wang et al. (2007) Drug-Induced Epigenetic Changes Produce Drug Tolerance. PLoS Biol, 5:e265Projects_Epigenetic_Reg_slo_files/Wang%20et%20al%202009.pdfProjects_Epigenetic_Reg_slo_files/Wang%20et%20al%202009.pdfProjects_Epigenetic_Reg_slo_files/Wang%20et%20al%202009.pdfProjects_Epigenetic_Reg_slo_files/Wang%20et%20al.%202007.pdfProjects_Epigenetic_Reg_slo_files/Wang%20et%20al.%202007.pdfshapeimage_6_link_0shapeimage_6_link_1shapeimage_6_link_2shapeimage_6_link_3shapeimage_6_link_4

Mechanism