Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-25604-5
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Funding
- ERC [740041]
- Spanish Ministerio de Economia y Competitividad [BFU2016-74961-P]
- Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation
- Federation of European Biochemical Societies (FEBS Long-Term Fellowship)
- European Union [800396]
- Juan de la Cierva-Formacion fellow from the Spanish Ministry of Science and Innovation [FJC2018-038233-I]
- Junta de Andalucia [DOC_00512]
- Unidad de Excelencia Maria de Maeztu [MDM-2016-0687]
- European Research Council (ERC) [740041] Funding Source: European Research Council (ERC)
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CTCF plays a critical role in animal development by regulating three-dimensional chromatin structure and enhancer-promoter interactions, essential for controlling the expression of thousands of genes. The architectural protein CTCF mediates chromatin looping and is enriched at the boundaries of topologically associating domains (TADs), impacting gene regulation during development. Loss of CTCF leads to disrupted chromatin structure and affects the expression of developmental regulators, highlighting its essential role in providing structural context for enhancer-promoter interactions.
CTCF is as an architectural protein involved in 3D genome folding; however its contribution to animal development has not been well characterized. Here the authors show that CTCF is not only pivotal for 3D chromatin structure and enhancer-promoter interactions in zebrafish, but it is also essential for controlling the expression of thousands of genes during development. 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.
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