We have developed genomic strategies to study the functional properties and molecular determinants of DNA replication origins (ORIs) in all cell types of the whole organism to determine the influence of hormonal conditions, developmental signals and the environment (Fig. 1). We found that ORI activity is compatible with multiple signatures although most of them tend to associate with chromatin states present in proximal promoters, TSS and 5’-end of genes. In addition, ORIs are enriched in the tandem arrays of GGN trinucleotides, which can for G4 structures. Our experimental approach is opening a new avenue to use mutants in the analysis of genome replication. We are combining the study of molecular determinants of ORIs with detailed analysis of the pre-RC dynamics during organ development.

Cell proliferation is crucial for organogenesis, which is determined by a strict control of gene expression patterns. We study chromatin dynamics along the cell cycle with special emphasis in two aspects: one, the regulation of cell proliferation potential, very related to the control of gene expression in G1 and G2, and the exit to differentiation, and another, related to the specific chromatin modifications in response to stress. The balance between the canonical histone H3.1 and the variant H3.3 serves to identify the cell population undergoing their last cell cycle before exit to differentiation because most of H3.1 is massively evicted in the last G2 phase (Fig. 2), which is longer in these cells.