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| Status |
Public on Aug 02, 2021 |
| Title |
CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression [RNA-seq] |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
CTCF is an 11-zinc-finger DNA-binding protein that acts as a transcriptional repressor and insulator, as well as an architectural protein required for 3D genome folding. CTCF mediates long-range chromatin looping and is enriched at the boundaries of topologically associating domains (TADs), which are sub-megabase chromatin structures composed of genomic regions with high contact frequency. Although CTCF is essential for cycling cells and developing embryos, its in vitro removal has only modest effects over gene expression, challenging the generally accepted idea that TADs facilitate enhancer-promoter interactions within gene regulatory landscapes. However, the effects of an altered CTCF-mediated chromatin structure on gene regulation in vivo are poorly understood. Here, we have generated a ctcf knockout mutant in zebrafish that allows us to monitor the effect of CTCF loss of function during embryo patterning and organogenesis. CTCF absence leads to a loss of chromatin structure in zebrafish embryos and affects the expression of thousands of genes, among them many developmental genes. In addition, we show that chromatin accessibility, both at CTCF sites and at developmental cis-regulatory elements (CREs), is severely compromised in ctcf mutants. Probing chromatin interactions from developmental genes at high resolution, we further demonstrate that promoters fail to fully establish long-range contacts with their associated regulatory landscapes, leading to altered gene expression patterns during development. Therefore, our results demonstrate that CTCF and TADs are essential to finetune gene expression during embryonic development, providing the structural basis for the establishment of developmental gene regulatory landscapes.
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| Overall design |
RNA-seq assays in wild-type and ctcf zebrafish mutants, at developmental stages 24 hpf and 48 hpf, with and without injection of tp53 morpholino
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| Contributor(s) |
Franke M, De la Calle-Mustienes E, Neto A, Almuedo-Castillo M, Irastorza-Azcárate I, Acemel RD, Tena JJ, Santos-Pereira JM, Gómez-Skarmeta JL |
| Citation(s) |
34518536 |
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| Submission date |
Aug 12, 2020 |
| Last update date |
Sep 15, 2021 |
| Contact name |
José M. Santos-Pereira |
| Organization name |
IBiS, Universidad de Sevilla-CSIC
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| Street address |
Avda. Manuel Siurot s/n
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| City |
Seville |
| ZIP/Postal code |
41013 |
| Country |
Spain |
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| Platforms (1) |
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| Samples (12)
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| GSM4724527 |
RNA-seq in zebrafish ctcf mutant embryos at 24hpf, replicate 1 |
| GSM4724528 |
RNA-seq in zebrafish ctcf mutant embryos at 24hpf, replicate 2 |
| GSM4724529 |
RNA-seq in zebrafish wild-type embryos at 24hpf, replicate 1 |
| GSM4724530 |
RNA-seq in zebrafish wild-type embryos at 24hpf, replicate 2 |
| GSM4724531 |
RNA-seq in zebrafish ctcf mutant embryos at 48hpf, injected with morpholino against tp53, replicate 1 |
| GSM4724532 |
RNA-seq in zebrafish ctcf mutant embryos at 48hpf, injected with morpholino against tp53, replicate 2 |
| GSM4724533 |
RNA-seq in zebrafish ctcf mutant embryos at 48hpf, replicate 1 |
| GSM4724534 |
RNA-seq in zebrafish ctcf mutant embryos at 48hpf, replicate 2 |
| GSM4724535 |
RNA-seq in zebrafish wild-type embryos at 48hpf, injected with morpholino against tp53, replicate 1 |
| GSM4724536 |
RNA-seq in zebrafish wild-type embryos at 48hpf, injected with morpholino against tp53, replicate 2 |
| GSM4724537 |
RNA-seq in zebrafish wild-type embryos at 48hpf, replicate 1 |
| GSM4724538 |
RNA-seq in zebrafish wild-type embryos at 48hpf, replicate 2 |
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| This SubSeries is part of SuperSeries: |
| GSE156099 |
CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression |
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| Relations |
| BioProject |
PRJNA656771 |
| SRA |
SRP277167 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE156094_RAW.tar |
213.9 Mb |
(http)(custom) |
TAR (of BW, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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