RNA polymerase II dynamics shape enhancer–promoter interactions
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RNA polymerase II dynamics shape enhancer–promoter interactions. / Barshad, Gilad; Lewis, James J.; Chivu, Alexandra G.; Abuhashem, Abderhman; Krietenstein, Nils; Rice, Edward J.; Ma, Yitian; Wang, Zhong; Rando, Oliver J.; Hadjantonakis, Anna Katerina; Danko, Charles G.
In: Nature Genetics, Vol. 55, 2023, p. 1370-1380.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - RNA polymerase II dynamics shape enhancer–promoter interactions
AU - Barshad, Gilad
AU - Lewis, James J.
AU - Chivu, Alexandra G.
AU - Abuhashem, Abderhman
AU - Krietenstein, Nils
AU - Rice, Edward J.
AU - Ma, Yitian
AU - Wang, Zhong
AU - Rando, Oliver J.
AU - Hadjantonakis, Anna Katerina
AU - Danko, Charles G.
N1 - Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023
Y1 - 2023
N2 - How enhancers control target gene expression over long genomic distances remains an important unsolved problem. Here we investigated enhancer–promoter communication by integrating data from nucleosome-resolution genomic contact maps, nascent transcription and perturbations affecting either RNA polymerase II (Pol II) dynamics or the activity of thousands of candidate enhancers. Integration of new Micro-C experiments with published CRISPRi data demonstrated that enhancers spend more time in close proximity to their target promoters in functional enhancer–promoter pairs compared to nonfunctional pairs, which can be attributed in part to factors unrelated to genomic position. Manipulation of the transcription cycle demonstrated a key role for Pol II in enhancer–promoter interactions. Notably, promoter-proximal paused Pol II itself partially stabilized interactions. We propose an updated model in which elements of transcriptional dynamics shape the duration or frequency of interactions to facilitate enhancer–promoter communication.
AB - How enhancers control target gene expression over long genomic distances remains an important unsolved problem. Here we investigated enhancer–promoter communication by integrating data from nucleosome-resolution genomic contact maps, nascent transcription and perturbations affecting either RNA polymerase II (Pol II) dynamics or the activity of thousands of candidate enhancers. Integration of new Micro-C experiments with published CRISPRi data demonstrated that enhancers spend more time in close proximity to their target promoters in functional enhancer–promoter pairs compared to nonfunctional pairs, which can be attributed in part to factors unrelated to genomic position. Manipulation of the transcription cycle demonstrated a key role for Pol II in enhancer–promoter interactions. Notably, promoter-proximal paused Pol II itself partially stabilized interactions. We propose an updated model in which elements of transcriptional dynamics shape the duration or frequency of interactions to facilitate enhancer–promoter communication.
U2 - 10.1038/s41588-023-01442-7
DO - 10.1038/s41588-023-01442-7
M3 - Journal article
C2 - 37430091
AN - SCOPUS:85164344000
VL - 55
SP - 1370
EP - 1380
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
ER -
ID: 360404604