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Computational characterization of chromatin domain boundary-associated genomic elements

Topologically associated domains (TADs) are 3D genomic structures with high internal interactions that play important roles in genome compaction and gene regulation. Their genomic locations and their association with CCCTC-binding factor (CTCF)-binding sites and transcription start sites (TSSs) were...

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Autores principales: Hong, Seungpyo, Kim, Dongsup
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737353/
https://www.ncbi.nlm.nih.gov/pubmed/28977568
http://dx.doi.org/10.1093/nar/gkx738
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author Hong, Seungpyo
Kim, Dongsup
author_facet Hong, Seungpyo
Kim, Dongsup
author_sort Hong, Seungpyo
collection PubMed
description Topologically associated domains (TADs) are 3D genomic structures with high internal interactions that play important roles in genome compaction and gene regulation. Their genomic locations and their association with CCCTC-binding factor (CTCF)-binding sites and transcription start sites (TSSs) were recently reported. However, the relationship between TADs and other genomic elements has not been systematically evaluated. This was addressed in the present study, with a focus on the enrichment of these genomic elements and their ability to predict the TAD boundary region. We found that consensus CTCF-binding sites were strongly associated with TAD boundaries as well as with the transcription factors (TFs) Zinc finger protein (ZNF)143 and Yin Yang (YY)1. TAD boundary-associated genomic elements include DNase I-hypersensitive sites, H3K36 trimethylation, TSSs, RNA polymerase II, and TFs such as Specificity protein 1, ZNF274 and SIX homeobox 5. Computational modeling with these genomic elements suggests that they have distinct roles in TAD boundary formation. We propose a structural model of TAD boundaries based on these findings that provides a basis for studying the mechanism of chromatin structure formation and gene regulation.
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spelling pubmed-57373532018-01-08 Computational characterization of chromatin domain boundary-associated genomic elements Hong, Seungpyo Kim, Dongsup Nucleic Acids Res Computational Biology Topologically associated domains (TADs) are 3D genomic structures with high internal interactions that play important roles in genome compaction and gene regulation. Their genomic locations and their association with CCCTC-binding factor (CTCF)-binding sites and transcription start sites (TSSs) were recently reported. However, the relationship between TADs and other genomic elements has not been systematically evaluated. This was addressed in the present study, with a focus on the enrichment of these genomic elements and their ability to predict the TAD boundary region. We found that consensus CTCF-binding sites were strongly associated with TAD boundaries as well as with the transcription factors (TFs) Zinc finger protein (ZNF)143 and Yin Yang (YY)1. TAD boundary-associated genomic elements include DNase I-hypersensitive sites, H3K36 trimethylation, TSSs, RNA polymerase II, and TFs such as Specificity protein 1, ZNF274 and SIX homeobox 5. Computational modeling with these genomic elements suggests that they have distinct roles in TAD boundary formation. We propose a structural model of TAD boundaries based on these findings that provides a basis for studying the mechanism of chromatin structure formation and gene regulation. Oxford University Press 2017-10-13 2017-08-23 /pmc/articles/PMC5737353/ /pubmed/28977568 http://dx.doi.org/10.1093/nar/gkx738 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Computational Biology
Hong, Seungpyo
Kim, Dongsup
Computational characterization of chromatin domain boundary-associated genomic elements
title Computational characterization of chromatin domain boundary-associated genomic elements
title_full Computational characterization of chromatin domain boundary-associated genomic elements
title_fullStr Computational characterization of chromatin domain boundary-associated genomic elements
title_full_unstemmed Computational characterization of chromatin domain boundary-associated genomic elements
title_short Computational characterization of chromatin domain boundary-associated genomic elements
title_sort computational characterization of chromatin domain boundary-associated genomic elements
topic Computational Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737353/
https://www.ncbi.nlm.nih.gov/pubmed/28977568
http://dx.doi.org/10.1093/nar/gkx738
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