The absence of specific sequence motifs marking the origins of replication has been a serious hindrance to the understanding of the mechanisms that regulate the initiation and the maintenance of the replication program in different eukaryotic cell types. Our wavelet-based pattern recognition methodology delineates replication domains where the replication timing profile is shaped as a U and its derivative as a N. Replication U-domains are robustly found in seven cell lines covering a significant portion (40-50%) of the human genome. We find that the compartmentalization of the human genome into autonomous replication U-domains comes along with an extensive remodelling of the 3-dimensional chromosome architecture during development or in specific diseases.