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CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression

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Item Type:Article
Title:CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression
Creators Name:Franke, M. and De la Calle-Mustienes, E. and Neto, A. and Almuedo-Castillo, M. and Irastorza-Azcarate, I. and Acemel, R.D. and Tena, J.J. and Santos-Pereira, J.M. and Gómez-Skarmeta, J.L.
Abstract: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.
Keywords:Body Patterning, CCCTC-Binding Factor, CRISPR-Cas Systems, Chromatin, Developmental Gene Expression Regulation, Genetic Enhancer Elements, Genetic Promoter Regions, Gene Knockout Techniques, Nonmammalian Embryo, Organogenesis, RNA-Seq, Zebrafish Proteins, Animals, Zebrafish
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:5415
Date:13 September 2021
Official Publication:https://doi.org/10.1038/s41467-021-25604-5
PubMed:View item in PubMed

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