title: A histone modification identifies a DNA element controlling slo BK channel gene expression in muscle.
abstract: The slo gene encodes the BK-type Ca(2+)-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.
authors.affiliation: a School of Biological Sciences, Nanyang Technological University , Singapore.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Li
authors.affiliation: b Department of Neuroscience and The Waggoner Center for Alcohol and Addiction Research , The University of Texas at Austin , Austin, Texas , USA.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ghezzi
authors.affiliation: c Department of Psychiatry , University of Illinois at Chicago and Jesse Brown VA Medical Center , Chicago , IL , USA.
authors.forename: Harish R
authors.initials: HR
authors.lastname: Krishnan
authors.affiliation: b Department of Neuroscience and The Waggoner Center for Alcohol and Addiction Research , The University of Texas at Austin , Austin, Texas , USA.
authors.forename: Jascha B
authors.initials: JB
authors.lastname: Pohl
authors.affiliation: b Department of Neuroscience and The Waggoner Center for Alcohol and Addiction Research , The University of Texas at Austin , Austin, Texas , USA.
authors.forename: Arun Y
authors.initials: AY
authors.lastname: Bohm
authors.affiliation: b Department of Neuroscience and The Waggoner Center for Alcohol and Addiction Research , The University of Texas at Austin , Austin, Texas , USA.
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Atkinson
mesh_terms: D000818:Animals; D019905:Benzyl Alcohol / Q000494:pharmacology; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004361:Drug Tolerance / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D042421:Histone Code; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects
chemical_list: D029721:Drosophila Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; C494844:slo protein, Drosophila; D019905:Benzyl Alcohol
keywords: Behavior; DNA element; Drosophila; histone marks; ion channel; transcription