Fig. 6.

Chromatin proteins modulate the relationship between genetics and gene expression. The existing framework (gray arrows) for explaining cardiac phenotype is that genetics and environmental stimulation are the driving regulators of gene expression, which in turn determines phenotype. Our data support this model, showing that cardiac gene expression does not correlate with phenotype across all genetic backgrounds due to contributions by chromatin regulatory inputs. Additionally, we build on this model (red arrows) showing that chromatin protein levels feedback to influence gene expression, based on our observation that gene expression “relatedness” is organ dependent. We further posit that there is a direct interaction between environmental stimuli and genetics, based on our observation that different genetic components are responsible for basal or isoproterenol-induced gene expression in the heart.