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

Nicholas P. Mullin, Joby Varghese, Douglas Colby, Julia M. Richardson, Greg M. Findlay, Ian Chambers (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
40 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)14-25
Number of pages12
JournalFEBS Letters
Issue number1
Early online date26 Oct 2020
Publication statusPublished - Jan 2021


  • DNA binding
  • casein kinase I
  • phosphorylation
  • self-renewal

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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