We review recent developments in mapping chromosomal contacts and compare emerging insights on chromosomal contact domain organization in Drosophila and mammalian cells. Potential scenarios leading to the observation of Hi-C domains and their association with the epigenomic context of the chromosomal elements involved are discussed. We argue that even though the mechanisms and precise physical structure underlying chromosomal domain demarcation are yet to be fully resolved, the implications to

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... enome regulation and genome evolution are profound. Specifically, we hypothesize that domains are facilitating genomic compartmentalization that support the implementation of complex, modular, and tissue specific transcriptional program in metazoa.