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Exploiting genetic variation to uncover rules of transcription factor binding and chromatin accessibility
Single-nucleotide variants that underlie phenotypic variation can affect chromatin occupancy of transcription factors (TFs). To delineate determinants of in vivo TF binding and chromatin accessibility, we introduce an approach that compares ChIP-seq and DNase-seq data sets from genetically divergent...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823854/ https://www.ncbi.nlm.nih.gov/pubmed/29472540 http://dx.doi.org/10.1038/s41467-018-03082-6 |
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author | Behera, Vivek Evans, Perry Face, Carolyne J. Hamagami, Nicole Sankaranarayanan, Laavanya Keller, Cheryl A. Giardine, Belinda Tan, Kai Hardison, Ross C. Shi, Junwei Blobel, Gerd A. |
author_facet | Behera, Vivek Evans, Perry Face, Carolyne J. Hamagami, Nicole Sankaranarayanan, Laavanya Keller, Cheryl A. Giardine, Belinda Tan, Kai Hardison, Ross C. Shi, Junwei Blobel, Gerd A. |
author_sort | Behera, Vivek |
collection | PubMed |
description | Single-nucleotide variants that underlie phenotypic variation can affect chromatin occupancy of transcription factors (TFs). To delineate determinants of in vivo TF binding and chromatin accessibility, we introduce an approach that compares ChIP-seq and DNase-seq data sets from genetically divergent murine erythroid cell lines. The impact of discriminatory single-nucleotide variants on TF ChIP signal enables definition at single base resolution of in vivo binding characteristics of nuclear factors GATA1, TAL1, and CTCF. We further develop a facile complementary approach to more deeply test the requirements of critical nucleotide positions for TF binding by combining CRISPR-Cas9-mediated mutagenesis with ChIP and targeted deep sequencing. Finally, we extend our analytical pipeline to identify nearby contextual DNA elements that modulate chromatin binding by these three TFs, and to define sequences that impact kb-scale chromatin accessibility. Combined, our approaches reveal insights into the genetic basis of TF occupancy and their interplay with chromatin features. |
format | Online Article Text |
id | pubmed-5823854 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58238542018-02-26 Exploiting genetic variation to uncover rules of transcription factor binding and chromatin accessibility Behera, Vivek Evans, Perry Face, Carolyne J. Hamagami, Nicole Sankaranarayanan, Laavanya Keller, Cheryl A. Giardine, Belinda Tan, Kai Hardison, Ross C. Shi, Junwei Blobel, Gerd A. Nat Commun Article Single-nucleotide variants that underlie phenotypic variation can affect chromatin occupancy of transcription factors (TFs). To delineate determinants of in vivo TF binding and chromatin accessibility, we introduce an approach that compares ChIP-seq and DNase-seq data sets from genetically divergent murine erythroid cell lines. The impact of discriminatory single-nucleotide variants on TF ChIP signal enables definition at single base resolution of in vivo binding characteristics of nuclear factors GATA1, TAL1, and CTCF. We further develop a facile complementary approach to more deeply test the requirements of critical nucleotide positions for TF binding by combining CRISPR-Cas9-mediated mutagenesis with ChIP and targeted deep sequencing. Finally, we extend our analytical pipeline to identify nearby contextual DNA elements that modulate chromatin binding by these three TFs, and to define sequences that impact kb-scale chromatin accessibility. Combined, our approaches reveal insights into the genetic basis of TF occupancy and their interplay with chromatin features. Nature Publishing Group UK 2018-02-22 /pmc/articles/PMC5823854/ /pubmed/29472540 http://dx.doi.org/10.1038/s41467-018-03082-6 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Behera, Vivek Evans, Perry Face, Carolyne J. Hamagami, Nicole Sankaranarayanan, Laavanya Keller, Cheryl A. Giardine, Belinda Tan, Kai Hardison, Ross C. Shi, Junwei Blobel, Gerd A. Exploiting genetic variation to uncover rules of transcription factor binding and chromatin accessibility |
title | Exploiting genetic variation to uncover rules of transcription factor binding and chromatin accessibility |
title_full | Exploiting genetic variation to uncover rules of transcription factor binding and chromatin accessibility |
title_fullStr | Exploiting genetic variation to uncover rules of transcription factor binding and chromatin accessibility |
title_full_unstemmed | Exploiting genetic variation to uncover rules of transcription factor binding and chromatin accessibility |
title_short | Exploiting genetic variation to uncover rules of transcription factor binding and chromatin accessibility |
title_sort | exploiting genetic variation to uncover rules of transcription factor binding and chromatin accessibility |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823854/ https://www.ncbi.nlm.nih.gov/pubmed/29472540 http://dx.doi.org/10.1038/s41467-018-03082-6 |
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