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| Status |
Public on Oct 22, 2019 |
| Title |
Inter-chromosomal enhancer-promoter interaction critical for the appropriate level of Tead4 gene expression at the blastocyst stage [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Although Tead4 is well-known to be critical for blastocyst development and trophoblast lineage differentiation, the higher-order chromatin organization around this gene remains poorly understood. We assayed long-range chromosomal interactions on the Tead4 promoter in mouse embryonic stem (ES) cells and trophoblast stem (TS) cells using the circular chromosome conformation capture (4C)-seq technique. We observed frequent overlaps of genomic regions interacting with the Tead4 promoter and open chromatin regions identified by FAIRE-seq in TS cells. By systematic reporter assays using ES and TS cells, we identified five genomic fragments possessing a TS-specific enhancer activity to the Tead4 promoter, consisting of two intra- and three inter-chromosomal loci relative to the Tead4 gene on chromosome 6. We established five mouse lines deleted with one of the five enhancer elements using CRISPR/Cas9 genome editing, and evaluated the effect of each of the enhancer deletions on the Tead4 gene expression at the blastocyst stage. We observed 35-50% decrease of the Tead4 expression in the blastocysts with heterozygous or homozygous deletion of an inter-chromosomally located enhancer on chromosome 19 compared to that in wild-type blastocysts, whereas the other four deletions did not affect the Tead4 expression level. Our results demonstrate that inter-chromosomal enhancer-promoter interaction bears a critical role in assuring the appropriate level of Tead4 gene expression at the trophoblast lineage specification.
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| Overall design |
RNA-seq was performed for the blastocystes homozygously or heterozygously deleted with the Region M on chromosome 19 and for the wild-type blastocysts. RNA-seq was also performed for the C57BL/6 mouse-derived ES and TS cells.
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| Contributor(s) |
Tomikawa J, Nakabayashi K |
| Citation(s) |
31777916 |
| Submission date |
Jul 28, 2019 |
| Last update date |
Jan 13, 2020 |
| Contact name |
Kazuhiko Nakabayashi |
| E-mail(s) |
nakabaya-k@ncchd.go.jp
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| Organization name |
National Research Institute for Child Health and Development
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| Department |
Department of Maternal-Fetal Biology
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| Street address |
2-10-1 Okura
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| City |
Setagaya |
| State/province |
Tokyo |
| ZIP/Postal code |
157-8535 |
| Country |
Japan |
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| Platforms (2) |
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| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE109252 |
Inter-chromosomal enhancer-promoter interaction critical for the appropriate level of Tead4 gene expression at the blastocyst stage |
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| Relations |
| BioProject |
PRJNA557045 |
| SRA |
SRP216609 |
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