Transcriptional decomposition reveals active chromatin architectures and cell specific regulatory interactions
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Transcriptional decomposition reveals active chromatin architectures and cell specific regulatory interactions. / Rennie, Sarah; Dalby, Maria; van Duin, Lucas; Andersson, Robin.
I: Nature Communications, Bind 9, 487, 2018.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
Y1 - 2018
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
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 487
ER -
ID: 195152781