Abstract The capability of a genome to produce the diversity of cell types present within a single human, or plant, is derived from the extraordinary regulatory mechanisms that have evolved to control the transcription and translation of nucleotide to protein. Similar mechanisms have also been coopted to allow organisms to plastically alter development in response to external environmental conditions. Environmentally mediated shifts in developmental trajectory are often mediated by epigenetic modifications that chemically and physically manipulate the genome, and in turn alter the expression of genes. While changes in gene regulation due to transcriptional cascades are often fleeting, epigenetic modifications can persist across cell divisions, and in some cases between generations. The evolutionary and health ramifications of epigenetic inheritance are still quite poorly understood, with a particular dearth of knowledge regarding how genetic variation alters epigenetic responses to the environment. I propose to leverage the rapid life cycle, vast phenotypic plasticity, genomic resources, and self-fertilizing capability of the Mimulus laciniatus plant model system to study the interactions between genetic variation and epigenetic inheritance. I hypothesize that local adaptation drives divergence in the genes and regulatory regions that mediate environmentally induced epigenetic inheritance, in turn generating natural variation in transgenerational gene expression and phenotypic plasticity. I will test this hypothesis with the following aims: I. Assess the contribution of genetic variation, transgenerational inheritance, and environmental conditions on the regulation of gene expression, DNA methylation, and development. II. Determine the genetic basis of natural variation for transgenerational inheritance to temperature regimes. III. Measure the role of transgenerational inheritance and “transgenerational x genetic” effects on plant survival and development in divergent field conditions.