In the nucleus of eukaryotic cells, DNA is folded in a three-dimensional (3D) architecture that is thought to orchestrate fundamental nuclear processes, including DNA replication, DNA repair, and transcription. An emerging paradigm in the field is that multi-valent interactions between DNA, RNAs, and proteins mediate so-called liquid-liquid phase transitions, which in turn mediate the spatial organization of chromatin in the nucleus. However, the exact nature and dynamics of these interactions, and how they contribute to shaping the 3D genome and its functions remain elusive. Here, we aim to tackle these fundamental yet largely unexplored questions, by integrating multiple omic datasets to unravel DNA-RNA-protein interactions and linking them to transcriptional changes that occur during the differentiation of embryonic stem cells towards neurons.