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Synopsis Epigenetic mechanisms are increasingly understood to have major impacts across ecology. However, one molecular epigenetic mechanism, DNA methylation, currently dominates the literature. A second mechanism, histone modification, is likely important to ecologically relevant phenotypes and thus warrants investigation, especially because molecular interplay between methylation and histone acetylation can strongly affect gene expression. There are a limited number of histone acetylation studies on non-model organisms, yet those that exist show that it can impact gene expression and phenotypic plasticity. Wild birds provide an excellent system to investigate histone acetylation, as free-living individuals must rapidly adjust to environmental change. Here, we screen histone acetylation in the house sparrow (Passer domesticus); we studied this species because DNA methylation was important in the spread of this bird globally. This species has one of the broadest geographic distributions in the world, and part of this success is related to the way that it uses methylation to regulate its gene expression. Here, we verify that a commercially available assay that was developed for mammals can be used in house sparrows. We detected high variance in histone acetylation among individuals in both liver and spleen tissue. Further, house sparrows with higher epigenetic potential in the Toll Like Receptor-4 (TLR-4) promoter (i.e., CpG content) had higher histone acetylation in liver. Also, there was a negative correlation between histone acetylation in spleen and TLR-4 expression. In addition to validating a method for measuring histone acetylation in wild songbirds, this study also shows that histone acetylation is related to epigenetic potential and gene expression, adding a new study option for ecological epigenetics.