Bibliographic Details
| Title: |
p53 Integrates Temporal WDR5 Inputs during Neuroectoderm and Mesoderm Differentiation of Mouse Embryonic Stem Cells |
| Authors: |
Qiang Li, Fengbiao Mao, Bo Zhou, Yuanhao Huang, Zhenhua Zou, Aaron D. denDekker, Jing Xu, Sean Hou, Jie Liu, Yali Dou, Rajesh C. Rao |
| Source: |
Cell Reports, Vol 30, Iss 2, Pp 465-480.e6 (2020) |
| Publisher Information: |
Elsevier, 2020. |
| Publication Year: |
2020 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
Biology (General), QH301-705.5 |
| More Details: |
Summary: 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. : How ubiquitous chromatin-associated proteins and transcription factors (TFs) regulate cell fate determination is poorly understood. Li et al. show that regulation of the broadly expressed TF p53 by the chromatin-associated protein WDR5 is required for neuroectoderm versus mesoderm lineage determination in mouse embryonic stem cells (ESCs). Keywords: WDR5, p53, chromatin, cell fate, embryonic stem cells, differentiation, retina, neuroectoderm, mesoderm, cardiomyocyte |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2211-1247 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2211124719316961; https://doaj.org/toc/2211-1247 |
| DOI: |
10.1016/j.celrep.2019.12.039 |
| Access URL: |
https://doaj.org/article/1e32d07bf5fe4e77a971975d984c9031 |
| Accession Number: |
edsdoj.1e32d07bf5fe4e77a971975d984c9031 |
| Database: |
Directory of Open Access Journals |
