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Phosphorylation of NANOG by casein kinase I regulates embryonic stem cell self‐renewal

The self‐renewal efficiency of mouse embryonic stem cells (ESCs) is determined by the concentration of the transcription factor NANOG. While NANOG binds thousands of sites in chromatin, the regulatory systems that control DNA binding are poorly characterised. Here, we show that NANOG is phosphorylat...

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Detalles Bibliográficos
Autores principales: Mullin, Nicholas P., Varghese, Joby, Colby, Douglas, Richardson, Julia M., Findlay, Greg M., Chambers, Ian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839479/
https://www.ncbi.nlm.nih.gov/pubmed/33107035
http://dx.doi.org/10.1002/1873-3468.13969
Descripción
Sumario:The self‐renewal efficiency of mouse embryonic stem cells (ESCs) is determined by the concentration of the transcription factor NANOG. While NANOG binds thousands of sites in chromatin, the regulatory systems that control DNA binding are poorly characterised. Here, we show that NANOG is phosphorylated by casein kinase I, and identify target residues. Phosphomimetic substitutions at phosphorylation sites within the homeodomain (S130 and S131) have site‐specific functional effects. Phosphomimetic substitution of S130 abolishes DNA binding by NANOG and eliminates LIF‐independent self‐renewal. In contrast, phosphomimetic substitution of S131 enhances LIF‐independent self‐renewal, without influencing DNA binding. Modelling the DNA–homeodomain complex explains the disparate effects of these phosphomimetic substitutions. These results indicate how phosphorylation may influence NANOG homeodomain interactions that underpin ESC self‐renewal.