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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...

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Autores principales: Narendra, Varun, Bulajić, Milica, Dekker, Job, Mazzoni, Esteban O., Reinberg, Danny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
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.
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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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