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CTCF-mediated topological boundaries during development foster appropriate gene regulation
The genome is organized into repeating topologically associated domains (TADs), each of which is spatially isolated from its neighbor by poorly understood boundary elements thought to be conserved across cell types. Here, we show that deletion of CTCF (CCCTC-binding factor)-binding sites at TAD and...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5238725/ https://www.ncbi.nlm.nih.gov/pubmed/28087711 http://dx.doi.org/10.1101/gad.288324.116 |
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author | Narendra, Varun Bulajić, Milica Dekker, Job Mazzoni, Esteban O. Reinberg, Danny |
author_facet | Narendra, Varun Bulajić, Milica Dekker, Job Mazzoni, Esteban O. Reinberg, Danny |
author_sort | Narendra, Varun |
collection | PubMed |
description | The genome is organized into repeating topologically associated domains (TADs), each of which is spatially isolated from its neighbor by poorly understood boundary elements thought to be conserved across cell types. Here, we show that deletion of CTCF (CCCTC-binding factor)-binding sites at TAD and sub-TAD topological boundaries that form within the HoxA and HoxC clusters during differentiation not only disturbs local chromatin domain organization and regulatory interactions but also results in homeotic transformations typical of Hox gene misregulation. Moreover, our data suggest that CTCF-dependent boundary function can be modulated by competing forces, such as the self-assembly of polycomb domains within the nucleus. Therefore, CTCF boundaries are not merely static structural components of the genome but instead are locally dynamic regulatory structures that control gene expression during development. |
format | Online Article Text |
id | pubmed-5238725 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-52387252017-06-15 CTCF-mediated topological boundaries during development foster appropriate gene regulation Narendra, Varun Bulajić, Milica Dekker, Job Mazzoni, Esteban O. Reinberg, Danny Genes Dev Research Communication The genome is organized into repeating topologically associated domains (TADs), each of which is spatially isolated from its neighbor by poorly understood boundary elements thought to be conserved across cell types. Here, we show that deletion of CTCF (CCCTC-binding factor)-binding sites at TAD and sub-TAD topological boundaries that form within the HoxA and HoxC clusters during differentiation not only disturbs local chromatin domain organization and regulatory interactions but also results in homeotic transformations typical of Hox gene misregulation. Moreover, our data suggest that CTCF-dependent boundary function can be modulated by competing forces, such as the self-assembly of polycomb domains within the nucleus. Therefore, CTCF boundaries are not merely static structural components of the genome but instead are locally dynamic regulatory structures that control gene expression during development. Cold Spring Harbor Laboratory Press 2016-12-15 /pmc/articles/PMC5238725/ /pubmed/28087711 http://dx.doi.org/10.1101/gad.288324.116 Text en © 2016 Narendra et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Communication Narendra, Varun Bulajić, Milica Dekker, Job Mazzoni, Esteban O. Reinberg, Danny CTCF-mediated topological boundaries during development foster appropriate gene regulation |
title | CTCF-mediated topological boundaries during development foster appropriate gene regulation |
title_full | CTCF-mediated topological boundaries during development foster appropriate gene regulation |
title_fullStr | CTCF-mediated topological boundaries during development foster appropriate gene regulation |
title_full_unstemmed | CTCF-mediated topological boundaries during development foster appropriate gene regulation |
title_short | CTCF-mediated topological boundaries during development foster appropriate gene regulation |
title_sort | ctcf-mediated topological boundaries during development foster appropriate gene regulation |
topic | Research Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5238725/ https://www.ncbi.nlm.nih.gov/pubmed/28087711 http://dx.doi.org/10.1101/gad.288324.116 |
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