Transcriptional decomposition reveals active chromatin architectures and cell specific regulatory interactions

Research output: Contribution to journalJournal articleResearchpeer-review

Transcriptional regulation is tightly coupled with chromosomal positioning and three-dimensional chromatin architecture. However, it is unclear what proportion of transcriptional activity is reflecting such organisation, how much can be informed by RNA expression alone and how this impacts disease. Here, we develop a computational transcriptional decomposition approach separating the proportion of expression associated with genome organisation from independent effects not directly related to genomic positioning. We show that positionally attributable expression accounts for a considerable proportion of total levels and is highly informative of topological associating domain activities and organisation, revealing boundaries and chromatin compartments. Furthermore, expression data alone accurately predict individual enhancer-promoter interactions, drawing features from expression strength, stabilities, insulation and distance. We characterise predictions in 76 human cell types, observing extensive sharing of domains, yet highly cell-type-specific enhancer-promoter interactions and strong enrichments in relevant trait-associated variants. Overall, our work demonstrates a close relationship between transcription and chromatin architecture.

Original languageEnglish
Article number487
JournalNature Communications
Number of pages16
Publication statusPublished - 2018

    Research areas

  • Chromatin/chemistry, Chromosome Mapping, Gene Expression Regulation, Gene Regulatory Networks, Humans, Models, Genetic, Promoter Regions, Genetic, RNA

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