BACKGROUND: SWI/SNF chromatin remodeling genes are required for normal acute responses to alcohol in C. elegans and are associated with alcohol use disorder in two human populations. In an effort to discover the downstream genes that are mediating this effect, we identified SWI/SNF-regulated genes in C. elegans. RESULTS: To identify SWI/SNF-regulated genes in adults, we compared mRNA expression in wild type and
swsn-1(
os22ts) worms under conditions that produce inactive
swsn-1 in mature cells. To identify SWI/SNF-regulated genes in neurons, we compared gene expression in
swsn-9(
ok1354) null mutant worms that harbor a neuronal rescue or a control construct. RNA sequencing was performed to an average depth of 25 million reads per sample using 50-base, paired-end reads. We found that 6813 transcripts were significantly differentially expressed between
swsn-1(
os22ts) mutants and wild-type worms and 2412 transcripts were significantly differentially expressed between
swsn-9(
ok1354) mutants and
swsn-9(
ok1354) mutants with neuronal rescue. We examined the intersection between these two datasets and identified 603 genes that were differentially expressed in the same direction in both comparisons; we defined these as SWI/SNF-regulated genes in neurons and in adults. Among the differentially expressed genes was
cbp-1, a C. elegans homolog of the mammalian CBP/p300 family of histone acetyltransferases. CBP has been implicated in the epigenetic regulation in response to alcohol in animal models and apolymorphism in the human CBP gene, CREBBP, has been associated with alcohol-related phenotypes. We found that
cbp-1 is required for the development of acute functional tolerance to alcohol in C. elegans. CONCLUSIONS: We identified 603 transcripts that were regulated by two different SWI/SNF complex subunits in adults and in neurons. The SWI/SNF-regulated genes were highly enriched for genes involved in membrane rafts, suggesting an important role for this membrane microdomain in the acute alcohol response. Among the differentially expressed genes was
cbp-1; CBP-1 homologs have been implicated in alcohol responses across phyla and we found that C. elegans
cbp-1 was required for the acute alcohol response in worms.