A histone modification identifies a DNA element controlling slo BK channel gene expression in muscle

Abstract

The slo gene encodes the BK-type Ca²⁺-activated K⁺ channels. In Drosophila, expression of slo is induced by organic solvent sedation (benzyl alcohol and ethanol), and this increase in neural slo expression contributes to the production of functional behavioral tolerance (inducible resistance) to these drugs. Within the slo promoter region, we observed that benzyl alcohol sedation produces a localized spike of histone acetylation over a 65-nucleotide (65-n) conserved DNA element called 55b. Changes in histone acetylation are commonly the consequence of transcription factor activity, and previously, a localized histone acetylation spike was used to successfully map a DNA element involved in benzyl alcohol-induced slo expression. To determine whether the 55b element was also involved in benzyl alcohol-induced neural expression of slo, we deleted it from the endogenous slo gene by homologous recombination. Flies lacking the 55b element were normal with respect to basal and benzyl alcohol-induced neural slo expression, the capacity to acquire and maintain functional tolerance, their threshold for electrically-induced seizures, and most slo-related behaviors. Removal of the 55b element did however increase the level of basal expression from the muscle/tracheal cell-specific slo core promoter and produced a slight increase in overall locomotor activity. We conclude that the 55b element is involved in control of slo expression from the muscle and tracheal-cell promoter but is not involved in the production of functional benzyl alcohol tolerance.

Keywords:

• Behavior
• DNA element
• Drosophila
• histone marks
• ion channel
• transcription

Acknowledgements

This work was supported by National Institutes of Health (NIH) R01 AA018037 (subgroup: NIAAA, title: Epigenetic Modification as a Mechanism to Produce Functional Tolerance). URL: http://www.niaaa.nih.gov. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.