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7C: Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs
BACKGROUND: Knowledge of the three-dimensional structure of the genome is necessary to understand how gene expression is regulated. Recent experimental techniques such as Hi-C or ChIA-PET measure long-range chromatin interactions genome-wide but are experimentally elaborate, have limited resolution...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814980/ https://www.ncbi.nlm.nih.gov/pubmed/31653198 http://dx.doi.org/10.1186/s12864-019-6088-0 |
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author | Ibn-Salem, Jonas Andrade-Navarro, Miguel A. |
author_facet | Ibn-Salem, Jonas Andrade-Navarro, Miguel A. |
author_sort | Ibn-Salem, Jonas |
collection | PubMed |
description | BACKGROUND: Knowledge of the three-dimensional structure of the genome is necessary to understand how gene expression is regulated. Recent experimental techniques such as Hi-C or ChIA-PET measure long-range chromatin interactions genome-wide but are experimentally elaborate, have limited resolution and such data is only available for a limited number of cell types and tissues. RESULTS: While ChIP-seq was not designed to detect chromatin interactions, the formaldehyde treatment in the ChIP-seq protocol cross-links proteins with each other and with DNA. Consequently, also regions that are not directly bound by the targeted TF but interact with the binding site via chromatin looping are co-immunoprecipitated and sequenced. This produces minor ChIP-seq signals at loop anchor regions close to the directly bound site. We use the position and shape of ChIP-seq signals around CTCF motif pairs to predict whether they interact or not. We implemented this approach in a prediction method, termed Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs (7C). We applied 7C to all CTCF motif pairs within 1 Mb in the human genome and validated predicted interactions with high-resolution Hi-C and ChIA-PET. A single ChIP-seq experiment from known architectural proteins (CTCF, Rad21, Znf143) but also from other TFs (like TRIM22 or RUNX3) predicts loops accurately. Importantly, 7C predicts loops in cell types and for TF ChIP-seq datasets not used in training. CONCLUSION: 7C predicts chromatin loops which can help to associate TF binding sites to regulated genes. Furthermore, profiling of hundreds of ChIP-seq datasets results in novel candidate factors functionally involved in chromatin looping. Our method is available as an R/Bioconductor package: http://bioconductor.org/packages/sevenC. |
format | Online Article Text |
id | pubmed-6814980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-68149802019-10-31 7C: Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs Ibn-Salem, Jonas Andrade-Navarro, Miguel A. BMC Genomics Research Article BACKGROUND: Knowledge of the three-dimensional structure of the genome is necessary to understand how gene expression is regulated. Recent experimental techniques such as Hi-C or ChIA-PET measure long-range chromatin interactions genome-wide but are experimentally elaborate, have limited resolution and such data is only available for a limited number of cell types and tissues. RESULTS: While ChIP-seq was not designed to detect chromatin interactions, the formaldehyde treatment in the ChIP-seq protocol cross-links proteins with each other and with DNA. Consequently, also regions that are not directly bound by the targeted TF but interact with the binding site via chromatin looping are co-immunoprecipitated and sequenced. This produces minor ChIP-seq signals at loop anchor regions close to the directly bound site. We use the position and shape of ChIP-seq signals around CTCF motif pairs to predict whether they interact or not. We implemented this approach in a prediction method, termed Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs (7C). We applied 7C to all CTCF motif pairs within 1 Mb in the human genome and validated predicted interactions with high-resolution Hi-C and ChIA-PET. A single ChIP-seq experiment from known architectural proteins (CTCF, Rad21, Znf143) but also from other TFs (like TRIM22 or RUNX3) predicts loops accurately. Importantly, 7C predicts loops in cell types and for TF ChIP-seq datasets not used in training. CONCLUSION: 7C predicts chromatin loops which can help to associate TF binding sites to regulated genes. Furthermore, profiling of hundreds of ChIP-seq datasets results in novel candidate factors functionally involved in chromatin looping. Our method is available as an R/Bioconductor package: http://bioconductor.org/packages/sevenC. BioMed Central 2019-10-25 /pmc/articles/PMC6814980/ /pubmed/31653198 http://dx.doi.org/10.1186/s12864-019-6088-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Ibn-Salem, Jonas Andrade-Navarro, Miguel A. 7C: Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs |
title | 7C: Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs |
title_full | 7C: Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs |
title_fullStr | 7C: Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs |
title_full_unstemmed | 7C: Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs |
title_short | 7C: Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs |
title_sort | 7c: computational chromosome conformation capture by correlation of chip-seq at ctcf motifs |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814980/ https://www.ncbi.nlm.nih.gov/pubmed/31653198 http://dx.doi.org/10.1186/s12864-019-6088-0 |
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