Elaborate non-random organization of human sperm chromosomes at different structural levels, starting from the DNA packing by protamines up to the higher-order chromosome configuration and nuclear positioning of chromosome territories, has been discovered. Here, we put forward a hypothesis that the unique genome architecture in sperm provides a mechanism for orchestrated unpacking and ordered activation of the male genome during fertilization, thus offering an additional level of epigenetic information that will be deciphered in the descendant cells.

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