論文 - 詳細
| RRC ID | 58710 |
|---|---|
| 著者 | Li Q, Mao F, Zhou B, Huang Y, Zou Z, denDekker AD, Xu J, Hou S, Liu J, Dou Y, Rao RC. |
| タイトル | p53 Integrates Temporal WDR5 Inputs during Neuroectoderm and Mesoderm Differentiation of Mouse Embryonic Stem Cells. |
| ジャーナル | Cell Rep |
| Abstract |
How ubiquitous transcription factors (TFs) coordinate temporal inputs from broadly expressed epigenetic factors to control cell fate remains poorly understood. Here, we uncover a molecular relationship between p53, an abundant embryonic TF, and WDR5, an essential member of the MLL chromatin modifying complex, that regulates mouse embryonic stem cell fate. Wild-type Wdr5 or transient Wdr5 knockout promotes a distinct pattern of global chromatin accessibility and spurs neuroectodermal differentiation through an RbBP5-dependent process in which WDR5 binds to, and activates transcription of, neural genes. Wdr5 rescue after its prolonged inhibition targets WDR5 to mesoderm lineage-specifying genes, stimulating differentiation toward mesoderm fates in a p53-dependent fashion. Finally, we identify a direct interaction between WDR5 and p53 that enables their co-recruitment to, and regulation of, genes known to control cell proliferation and fate. Our results unmask p53-dependent mechanisms that temporally integrate epigenetic WDR5 inputs to drive neuroectoderm and mesoderm differentiation from pluripotent cells. |
| 巻・号 | 30(2) |
| ページ | 465-480.e6 |
| 公開日 | 2020-1-14 |
| DOI | 10.1016/j.celrep.2019.12.039 |
| PII | S2211-1247(19)31696-1 |
| PMID | 31940490 |
| PMC | PMC7024586 |
| MeSH | Animals Cell Differentiation Humans Intracellular Signaling Peptides and Proteins / metabolism* Mesoderm / physiology* Mice Mouse Embryonic Stem Cells / metabolism* Neural Plate / physiology* Tumor Suppressor Protein p53 / metabolism* |
| IF | 8.109 |
| 引用数 | 0 |
| 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 | 50 |
| 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 | |
| ヒト・動物細胞 | Rx-GFP K/I EB5(AES0145) |