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p53 Integrates Temporal WDR5 Inputs during Neuroectoderm and Mesoderm Differentiation of Mouse Embryonic Stem Cells.
Li, Qiang; Mao, Fengbiao; Zhou, Bo; Huang, Yuanhao; Zou, Zhenhua; denDekker, Aaron D; Xu, Jing; Hou, Sean; Liu, Jie; Dou, Yali; Rao, Rajesh C.
Afiliação
  • Li Q; Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, MI, USA.
  • Mao F; Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Zhou B; Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Huang Y; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Zou Z; Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
  • denDekker AD; Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Xu J; Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Hou S; Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, MI, USA.
  • Liu J; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Dou Y; Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
  • Rao RC; Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA; Taubman Institute, University of Michigan, Ann Arbor, MI, USA;
Cell Rep ; 30(2): 465-480.e6, 2020 01 14.
Article em En | MEDLINE | ID: mdl-31940490
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteína Supressora de Tumor p53 / Peptídeos e Proteínas de Sinalização Intracelular / Placa Neural / Células-Tronco Embrionárias Murinas / Mesoderma Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteína Supressora de Tumor p53 / Peptídeos e Proteínas de Sinalização Intracelular / Placa Neural / Células-Tronco Embrionárias Murinas / Mesoderma Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article