| 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
|
| リソース情報 |
| ヒト・動物細胞 |
Rx-GFP K/I EB5(AES0145) |
