Identifying synergistic high-order 3D chromatin conformations from genome-scale nanopore concatemer sequencing
| العنوان: | Identifying synergistic high-order 3D chromatin conformations from genome-scale nanopore concatemer sequencing |
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| المؤلفون: | Aditya S. Deshpande, Netha Ulahannan, Matthew Pendleton, Xiaoguang Dai, Lynn Ly, Julie M. Behr, Stefan Schwenk, Will Liao, Michael A. Augello, Carly Tyer, Priyesh Rughani, Sarah Kudman, Huasong Tian, Hannah G. Otis, Emily Adney, David Wilkes, Juan Miguel Mosquera, Christopher E. Barbieri, Ari Melnick, David Stoddart, Daniel J. Turner, Sissel Juul, Eoghan Harrington, Marcin Imieliński |
| المصدر: | Nature Biotechnology. 40:1488-1499 |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Nanopore Sequencing, Nanopores, Androgens, Biomedical Engineering, Humans, Molecular Medicine, Bioengineering, Applied Microbiology and Biotechnology, Chromatin, Transcription Factors, Biotechnology |
| الوصف: | High-order three-dimensional (3D) interactions between more than two genomic loci are common in human chromatin, but their role in gene regulation is unclear. Previous high-order 3D chromatin assays either measure distant interactions across the genome or proximal interactions at selected targets. To address this gap, we developed Pore-C, which combines chromatin conformation capture with nanopore sequencing of concatemers to profile proximal high-order chromatin contacts at the genome scale. We also developed the statistical method Chromunity to identify sets of genomic loci with frequencies of high-order contacts significantly higher than background ('synergies'). Applying these methods to human cell lines, we found that synergies were enriched in enhancers and promoters in active chromatin and in highly transcribed and lineage-defining genes. In prostate cancer cells, these included binding sites of androgen-driven transcription factors and the promoters of androgen-regulated genes. Concatemers of high-order contacts in highly expressed genes were demethylated relative to pairwise contacts at the same loci. Synergies in breast cancer cells were associated with tyfonas, a class of complex DNA amplicons. These results rigorously link genome-wide high-order 3D interactions to lineage-defining transcriptional programs and establish Pore-C and Chromunity as scalable approaches to assess high-order genome structure. |
| تدمد: | 1546-1696 1087-0156 |
| DOI: | 10.1038/s41587-022-01289-z |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fb8ee58670be9489c6175a124e6506d6 https://doi.org/10.1038/s41587-022-01289-z |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....fb8ee58670be9489c6175a124e6506d6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461696 10870156 |
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| DOI: | 10.1038/s41587-022-01289-z |