Fabiana Patalano

• Patalano, Fabiana; Sandve, Simen Rød; Aasland, Rein & Paulsen, Jonas (2025). TAD conservation in vertebrate genomes is driven by stabilising selection. BMC Biology. 23(1). doi: 10.1186/s12915-025-02362-0. Full text in Research Archive Show summary

  Background Topologically associating domains (TADs) are fundamental structural and gene regulatory components of chromatin defined by regions of high intra-domain contact frequency. Though TADs are found across diverse metazoans, the extent of their evolutionary conservation is still debated. Results Here, we investigated the evolutionary conservation of TADs by analysing Hi-C data from 12 vertebrate species. We examined TAD numbers, borders, and gene positioning within TADs. We found that TAD features are all highly conserved across species, but decrease with evolutionary distance. Nevertheless, modelling TAD evolution using Ornstein–Uhlenbeck (OU) process revealed strong stabilising selection signatures for TAD number within the majority of syntenic blocks. These syntenic blocks under selection were enriched for highly conserved noncoding elements associated with developmental gene regulation (genomic regulatory blocks). However, strong signatures for stabilising selection for TAD numbers were also found independent of genomic regulatory blocks or genes with non-developmental functions. Conclusions These findings improve our understanding of TAD conservation and highlight stabilising selection as an important driver in 3D genome evolution. Although selection on TAD structures is pronounced for developmental genes, our findings highlight the importance of TADs in genome and organismal functions beyond developmental biology.

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• Paulsen, Jonas & Patalano, Fabiana (2023). Comparing Synteny and 3D Chromatin Architecture: Insights into structure evolutionary patterns and speciation in vertebrates. Full text in Research Archive
• Patalano, Fabiana (2025). Evolutionary conservation and gene regulatory implications of 3D genome compartmentalization. Universitetet i Oslo. Full text in Research Archive Show summary

  The human genome, nearly two meters of DNA and six billion bases, is compacted into a micrometer-sized nucleus. This organization is not random and is important for cell functions. This thesis focuses on two key levels of compartmentalization: Topologically Associating Domains (TADs) which are regions that interact more within themselves than with other regions, and compartments, which segregates active chromatin (A) from inactive chromatin (B). This work explores: - Evolutionary Conservation: by comparing TADs across 12 vertebrate species, we found that many TAD features are evolutionarily conserved. We further adapted an evolutionary model that provided evidence for stabilizing selection for TAD number within most syntenic regions. - Functional implications of compartment switching: consequences of compartmentalization changes in breast epithelial cells were analyzed following HP1a knockdown and TGFb treatment, both relevant to cancer. Removing HP1a led to a more open, active chromatin state, while TGFb induced a more closed, repressive state. In both cases, switches were linked to a dysregulation of cancer-related genes. In summary, this thesis provides new insights into the central role of genome compartmentalization in defining the structure and function of the 3D genome across both evolutionary and dynamic timescale, highlighting its key role in gene regulation, development, and disease.

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