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CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression
Coordinated chromatin interactions between enhancers and promoters are critical for gene regulation. The architectural protein CTCF mediates chromatin looping and is enriched at the boundaries of topologically associating domains (TADs), which are sub-megabase chromatin structures. In vitro CTCF dep...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438036/ https://www.ncbi.nlm.nih.gov/pubmed/34518536 http://dx.doi.org/10.1038/s41467-021-25604-5 |
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author | Franke, Martin De la Calle-Mustienes, Elisa Neto, Ana Almuedo-Castillo, María Irastorza-Azcarate, Ibai Acemel, Rafael D. Tena, Juan J. Santos-Pereira, José M. Gómez-Skarmeta, José L. |
author_facet | Franke, Martin De la Calle-Mustienes, Elisa Neto, Ana Almuedo-Castillo, María Irastorza-Azcarate, Ibai Acemel, Rafael D. Tena, Juan J. Santos-Pereira, José M. Gómez-Skarmeta, José L. |
author_sort | Franke, Martin |
collection | PubMed |
description | Coordinated chromatin interactions between enhancers and promoters are critical for gene regulation. The architectural protein CTCF mediates chromatin looping and is enriched at the boundaries of topologically associating domains (TADs), which are sub-megabase chromatin structures. In vitro CTCF depletion leads to a loss of TADs but has only limited effects over gene expression, challenging the concept that CTCF-mediated chromatin structures are a fundamental requirement for gene regulation. However, how CTCF and a perturbed chromatin structure impacts gene expression during development remains poorly understood. Here we link the loss of CTCF and gene regulation during patterning and organogenesis in a ctcf knockout zebrafish model. CTCF absence leads to loss of chromatin structure and affects the expression of thousands of genes, including many developmental regulators. Our results demonstrate the essential role of CTCF in providing the structural context for enhancer-promoter interactions, thus regulating developmental genes. |
format | Online Article Text |
id | pubmed-8438036 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84380362021-10-22 CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression Franke, Martin De la Calle-Mustienes, Elisa Neto, Ana Almuedo-Castillo, María Irastorza-Azcarate, Ibai Acemel, Rafael D. Tena, Juan J. Santos-Pereira, José M. Gómez-Skarmeta, José L. Nat Commun Article Coordinated chromatin interactions between enhancers and promoters are critical for gene regulation. The architectural protein CTCF mediates chromatin looping and is enriched at the boundaries of topologically associating domains (TADs), which are sub-megabase chromatin structures. In vitro CTCF depletion leads to a loss of TADs but has only limited effects over gene expression, challenging the concept that CTCF-mediated chromatin structures are a fundamental requirement for gene regulation. However, how CTCF and a perturbed chromatin structure impacts gene expression during development remains poorly understood. Here we link the loss of CTCF and gene regulation during patterning and organogenesis in a ctcf knockout zebrafish model. CTCF absence leads to loss of chromatin structure and affects the expression of thousands of genes, including many developmental regulators. Our results demonstrate the essential role of CTCF in providing the structural context for enhancer-promoter interactions, thus regulating developmental genes. Nature Publishing Group UK 2021-09-13 /pmc/articles/PMC8438036/ /pubmed/34518536 http://dx.doi.org/10.1038/s41467-021-25604-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Franke, Martin De la Calle-Mustienes, Elisa Neto, Ana Almuedo-Castillo, María Irastorza-Azcarate, Ibai Acemel, Rafael D. Tena, Juan J. Santos-Pereira, José M. Gómez-Skarmeta, José L. CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression |
title | CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression |
title_full | CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression |
title_fullStr | CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression |
title_full_unstemmed | CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression |
title_short | CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression |
title_sort | ctcf knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438036/ https://www.ncbi.nlm.nih.gov/pubmed/34518536 http://dx.doi.org/10.1038/s41467-021-25604-5 |
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