Speciation depends on the establishment of reproductive barriers that allow populations to diverge from each other. Such divergence may involve protein sequence, copy number, or expression changes that are predicted to result in dosage-dependent effects. In plants, such as Arabidopsis thaliana and A. arenosa, postzygotic species barriers often affect seed abortion, and hybrid failure resembles that of interploidy crosses where the paternal genome is in excess. We used this species pair to explore the relationship between hybrid incompatibility and gene silencing. In incompatible crosses, the normally silenced and heterochromatic element ATHILA was expressed from the paternal, but not maternal, chromosomes. Three Polycomb-regulated genes; PHERES1, MEIDOS, and MEDEA, were also induced. At PHERES1, maternal imprinting of the promoter was disrupted, and paternal imprinting of MEDEA appeared to be lost. The rate of hybrid seed lethality was sensitive to parental genome dosage, and gene activation was proportional to the dosage of parental genomes. A causal link was established between PHE1 and hybrid seed failure; a transposon-induced disruption of PHE1 significantly improved fertility. We propose that the dosage-dependent regulation of chromatin could be a universal phenomenon affecting lethality in interspecies hybrids.