| Autor: |
Fernandes, Liane P., Enriquez-Gasca, Rocio, Gould, Poppy A., Holt, James H., Conde, Lucia, Ecco, Gabriela, Herrero, Javier, Gifford, Robert, Trono, Didier, Kassiotis, George, Rowe, Helen M. |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Science Advances |
| ISSN: |
2375-2548 |
| Popis: |
Mammalian genomes are a battleground for genetic conflict between repetitive elements and KRAB-zinc finger proteins (KZFPs). We asked whether KZFPs can regulate cell fate by using ZFP819, which targets a satellite DNA array, ZP3AR. ZP3AR coats megabase regions of chromosome 7 encompassing genes encoding ZSCAN4, a master transcription factor of totipotency. Depleting ZFP819 in mouse embryonic stem cells (mESCs) causes them to transition to a 2-cell (2C)–like state, whereby the ZP3AR array switches from a poised to an active enhancer state. This is accompanied by a global erosion of heterochromatin roadblocks, which we link to decreased SETDB1 stability. These events result in transcription of active LINE-1 elements and impaired differentiation. In summary, ZFP819 and TRIM28 partner up to close chromatin across Zscan4 , to promote exit from totipotency. We propose that satellite DNAs may control developmental fate transitions by barcoding and switching off master transcription factor genes. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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