PUBLICATION
CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression
- Authors
- Franke, M., De la Calle-Mustienes, E., Neto, A., Almuedo-Castillo, M., Irastorza-Azcarate, I., Acemel, R.D., Tena, J.J., Santos-Pereira, J.M., Gómez-Skarmeta, J.L.
- ID
- ZDB-PUB-210915-2
- Date
- 2021
- Source
- Nature communications 12: 5415 (Journal)
- Registered Authors
- de la Calle-Mustienes, Elisa, Gómez-Skarmeta, José Luis, Neto, Ana, Tena, Juan
- Keywords
- none
- Datasets
- GEO:GSE156097, GEO:GSE156094, GEO:GSE156095, GEO:GSE156099, GEO:GSE156096, GEO:GSE156098, GEO:GSE175706
- MeSH Terms
-
- Animals
- Body Patterning/genetics
- CCCTC-Binding Factor/deficiency
- CCCTC-Binding Factor/genetics*
- CRISPR-Cas Systems
- Chromatin/genetics
- Chromatin/metabolism
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism*
- Enhancer Elements, Genetic/genetics
- Gene Expression Regulation, Developmental*
- Gene Knockout Techniques/methods*
- Organogenesis/genetics
- Promoter Regions, Genetic/genetics
- RNA-Seq/methods
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/genetics*
- PubMed
- 34518536 Full text @ Nat. Commun.
Citation
Franke, M., De la Calle-Mustienes, E., Neto, A., Almuedo-Castillo, M., Irastorza-Azcarate, I., Acemel, R.D., Tena, J.J., Santos-Pereira, J.M., Gómez-Skarmeta, J.L. (2021) CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression. Nature communications. 12:5415.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping