The first half of the 20th century was an important time for the scientific discipline of genetics in Japan (Iida, 2010). Hithoshi Kihara (1893–1986) was one of the pioneering researchers who helped to develop the field. He was the first to define the genome as the minimal set of chromosomes that is required for the fitness of a species and he also discovered sex chromosomes in plants. However, the achievement that made him internationally renowned was the development of seedless watermelon (Kihara, 1951). Kihara realized that triploid plants produce seedless fruits, which could be a desirable trait for certain crops. Therefore, he set out to create a triploid watermelon. To do this, he first obtained a tetraploid plant by treating a normal diploid with colchicine, a technique that was discovered shortly before Kiara’s watermelon experiment (Nebel, 1937). Next, he pollinated the tetraploid with pollen from a diploid. This yielded triploid progeny that did not produce seeds. Nowadays, seedless watermelons are still produced similarly. However, there is still a lot that we do not understand. The tetraploid progenitor of triploid watermelon exhibits many phenotypic differences as compared with their diploid counterparts. As yet, it remains enigmatic what causes these differences. Duplication of the genome might lead to rearrangements of the chromatin, because the nucleus needs to accommodate a doubled number of chromosomes. Although the exact effect of chromatin organization on gene regulation is not fully unraveled, it is clear that transcriptional activity is affected by the way the genome is folded (Doğan and Liu, 2018). Hence, altered chromatin organization might (partly) underlie the phenotypic differences in polyploids. In this issue, Marleny Garcia-Lozano and colleagues investigated the effect of genome doubling on chromatin conformation in watermelon. To understand the effect of doubling the number of chromosomes, the authors compared diploid watermelon with an isogenic tetraploid line. Compared to their diploid counterparts, the tetraploid plants had bigger seeds, bigger leaves, and a thicker stem with more and larger trichomes (Figure 1), phenotypes often seen in polyploids. To investigate how the chromatin is organized in diploid and tetraploid plants, the authors employed the Hi-C chromosome conformation capture technique. This technique crosslinks and ligates interacting chromatin fragments, followed by high-throughput sequencing, and is used to identify long-range physical interactions. They found that the interactions between genomic regions were different: in the tetraploid the chromosomes showed a higher number of interactions than in the diploid, especially between regions from different chromosomes. In addition to the chromatin interaction differences, the Hi-C results showed that the chromatin of tetraploid watermelon was organized differently than the chromatin in diploid plants. In eukaryotes, chromatin is divided into two spatially segregated compartments. The chromatin that occupies the interior nuclear space forms the transcriptionally active A compartment, whereas chromatin that resides at the nuclear periphery forms the less active B compartment. In tetraploid watermelon, several chromosomal regions had switched compartments. The authors found that chromatin organization also differed at lower levels of organization. Within the A and B compartments, chromatin is organized in megabase-sized clusters called topologically associated domains (TADs). TADs are demarcated by boundaries that function as insulators. As a result, DNA sequences within a TAD physically interact with each other more frequently than with sequences outside the TAD. The authors identified the boundaries of TADs in diploid and tetraploid watermelon and found that of 346 boundaries, 93 were differential between the two watermelon lines. Besides improved traits such as larger leaves, fruits, and flowers, polyploids can better deal with stressful environments. Therefore, polyploidy has played a key role in plant breeding for many years, and as climate change continues, polyploid crops might become increasingly important. Garcia-Lozano and colleagues found that the presence of a greater number of chromosomes alters the three-dimensional structure of the genome and affects interactions between genomic regions in watermelon. However, it is unclear how the altered chromatin organization affects the phenotype of watermelon after genome duplication. In addition to chromatin organization differences, the authors observed differences in the transcriptome and methylome between diploid and tetraploid watermelon. Seventy years after Kihara’s discovery, there is still a lot to learn about polyploid watermelon.