Transcriptional decomposition reveals active chromatin architectures and cell specific regulatory interactions

TY - JOUR

T1 - Transcriptional decomposition reveals active chromatin architectures and cell specific regulatory interactions

AU - Rennie, Sarah

AU - Dalby, Maria

AU - van Duin, Lucas

AU - Andersson, Robin

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

KW - Chromatin/chemistry

KW - Chromosome Mapping

KW - Gene Expression Regulation

KW - Gene Regulatory Networks

KW - Humans

KW - Models, Genetic

KW - Promoter Regions, Genetic

KW - RNA

U2 - 10.1038/s41467-017-02798-1

DO - 10.1038/s41467-017-02798-1

M3 - Journal article

C2 - 29402885

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

M1 - 487

ER -