The Emerging Sequence Grammar of 3D Genome Organisation

The multiplexed layers of regulatory processes and mechanisms within a cell are, to a degree, encoded in our genome. Unravelling the relationship between DNA sequence and molecular processes is crucial for understanding evolution, interpreting and predicting the consequences of genomic variation. Furthermore, understanding the extent to which DNA sequence contributes to the genome organisation can help reveal the aspects more influenced by other factors. Therefore, here we provide a succinct summary of the emerging genomic sequence code or “grammar” of genomic contact formation and 3D genome organisation. Drawing on different types of evidence from multiple disciplines, from large-scale genomic studies, biochemical in vitro assays, and computational analyses utilising machine learning and other modelling techniques, we aim to inform future research on the present associations between 3D genome organisation and sequence.