ABSTRACT
Gene transcription is influenced by favourable chromosome positioning and chromatin architectures bringing regulatory elements in close proximity. However, it is unclear to what extent transcription is attributable to topological organisation or to gene-specific regulatory programs. Here, we develop a strategy to transcriptionally decompose expression data into two main components reflecting the positional relationship of neighbouring transcriptional units and effects independent from their positioning. We demonstrate that the positionally dependent component is highly informative of topological domain activity and organisation, revealing boundaries and chromatin compartments. Furthermore, features derived from transcriptional components can accurately predict individual chromatin interactions. We systematically investigate regulatory interactions and observe different transcriptional attributes governing long-and short-range interactions. Finally, we assess differences in regulatory organisations across 76 human cell types. In all, we demonstrate a close relationship between transcription and topological chromatin architecture and provide an unprecedented resource for investigations of regulatory organisations across cell types.