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The desert plant Zygophyllum dumosum displays unique epigenetic constraints, not found in other perennial desert plants, namely, it possesses mono- but not di- and tri-methylated histone H3 at lysine 9 (H3K9). We investigated the proposal that lack of dimethylated H3K9 (H3K9me2) is not restricted to Z. dumosum, but a feature uniquely evolved in the Zygophyllaceae. To this end, we analyzed the state of H3K9me2 in various species including Z. simplex (annual), Peganum harmala (hemicryptophyte), Nitraria retusa (shrub) and Balanites aegyptiaca (tree) from the Negev Desert (Israel) and Larrea tridentata (creosote bush), a prominent species in the Mojave, Sonoran, and Chihuahuan Deserts of western North America. All but one of these plants showed dimethylation of H3 at lysine 4 (H3K4me2), but no detectable levels of H3K9me2. The exception was Nitraria retusa, recently separated from the Zygophyllaceae family, which possesses H3K9me2, further supporting its partition into a distinct family (Nitrariaceae). Interestingly, the analysis of Krameria cistoidea (Krameriaceae), which is listed under the Zygophyllales, showed the presence of H3K9me2. It appears that lack of H3K9me2 has uniquely evolved in the Zygophyllaceae (sensu stricto), suggesting that this phenomenon has a strong genetic background. Thus, epigenetic information revealed for Zygophyllaceae can be useful to phylogenetic approaches.