論文 - 詳細
| RRC ID | 56186 |
|---|---|
| 著者 | Kolundzic E, Ofenbauer A, Bulut SI, Uyar B, Baytek G, Sommermeier A, Seelk S, He M, Hirsekorn A, Vucicevic D, Akalin A, Diecke S, Lacadie SA, Tursun B. |
| タイトル | FACT Sets a Barrier for Cell Fate Reprogramming in Caenorhabditis elegans and Human Cells. |
| ジャーナル | Dev Cell |
| Abstract |
The chromatin regulator FACT (facilitates chromatin transcription) is essential for ensuring stable gene expression by promoting transcription. In a genetic screen using Caenorhabditis elegans, we identified that FACT maintains cell identities and acts as a barrier for transcription factor-mediated cell fate reprogramming. Strikingly, FACT's role as a barrier to cell fate conversion is conserved in humans as we show that FACT depletion enhances reprogramming of fibroblasts. Such activity is unexpected because FACT is known as a positive regulator of gene expression, and previously described reprogramming barriers typically repress gene expression. While FACT depletion in human fibroblasts results in decreased expression of many genes, a number of FACT-occupied genes, including reprogramming-promoting factors, show increased expression upon FACT depletion, suggesting a repressive function of FACT. Our findings identify FACT as a cellular reprogramming barrier in C. elegans and humans, revealing an evolutionarily conserved mechanism for cell fate protection. |
| 巻・号 | 46(5) |
| ページ | 611-626.e12 |
| 公開日 | 2018-9-10 |
| DOI | 10.1016/j.devcel.2018.07.006 |
| PII | S1534-5807(18)30559-8 |
| PMID | 30078731 |
| PMC | PMC6137076 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Differentiation Cell Lineage Cells, Cultured Cellular Reprogramming* Chromatin / genetics Chromatin / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Fibroblasts / cytology Fibroblasts / metabolism Gene Expression Regulation* High Mobility Group Proteins / genetics High Mobility Group Proteins / metabolism* Humans Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / physiology* Transcriptional Elongation Factors / genetics Transcriptional Elongation Factors / metabolism* Transcriptome |
| IF | 9.19 |
| 引用数 | 15 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 30 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1873 tm2539 |