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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
High-resolution targeted 3C interrogation of cis-regulatory element organization at genome-wide scale
Nature Communications, Volume 12, No. 1, Article 531, Year 2021
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Description
Chromosome conformation capture (3C) provides an adaptable tool for studying diverse biological questions. Current 3C methods generally provide either low-resolution interaction profiles across the entire genome, or high-resolution interaction profiles at limited numbers of loci. Due to technical limitations, generation of reproducible high-resolution interaction profiles has not been achieved at genome-wide scale. Here, to overcome this barrier, we systematically test each step of 3C and report two improvements over current methods. We show that up to 30% of reporter events generated using the popular in situ 3C method arise from ligations between two individual nuclei, but this noise can be almost entirely eliminated by isolating intact nuclei after ligation. Using Nuclear-Titrated Capture-C, we generate reproducible high-resolution genome-wide 3C interaction profiles by targeting 8055 gene promoters in erythroid cells. By pairing high-resolution 3C interaction calls with nascent gene expression we interrogate the role of promoter hubs and super-enhancers in gene regulation. © 2021, The Author(s).
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC7822813/bin/41467_2020_20809_MOESM1_ESM.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC7822813/bin/41467_2020_20809_MOESM2_ESM.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC7822813/bin/41467_2020_20809_MOESM3_ESM.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC7822813/bin/41467_2020_20809_MOESM4_ESM.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC7822813/bin/41467_2020_20809_MOESM5_ESM.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC7822813/bin/41467_2020_20809_MOESM6_ESM.xlsx
Authors & Co-Authors
Beagrie, Robert A.
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
Gosden, Matthew E.
United Kingdom, Oxford
Mrc Molecular Haematology Unit
Telenius, Jelena M.
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
De Ornellas, Sara
United Kingdom, Oxford
Mrc Molecular Haematology Unit
United Kingdom, Oxford
University of Oxford
Sergeant, Martin J.
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
Kerry, Jon
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
Shivalingam, Arun
United Kingdom, Oxford
University of Oxford
El-Sagheer, Afaf Helmy
United Kingdom, Oxford
University of Oxford
Oudelaar, Aukje Marieke
United Kingdom, Oxford
Mrc Molecular Haematology Unit
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
Brown, Tom
United Kingdom, Oxford
University of Oxford
Buckle, Veronica J.
United Kingdom, Oxford
Mrc Molecular Haematology Unit
Davies, James O.J.
United Kingdom, Oxford
Mrc Molecular Haematology Unit
Hughes, Jim R.
United Kingdom, Oxford
Mrc Molecular Haematology Unit
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
Statistics
Citations: 23
Authors: 13
Affiliations: 4
Identifiers
Doi:
10.1038/s41467-020-20809-6
ISSN:
20411723
Research Areas
Cancer
Genetics And Genomics