A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal

Alessia Gagliardi, Nicholas P Mullin, Zi Ying Tan, Douglas Colby, Anastasia I Kousa, Florian Halbritter, Jason T Weiss, Anastasia Felker, Karel Bezstarosti, Rebecca Favaro, Jeroen Demmers, Silvia K Nicolis, Simon R Tomlinson, Raymond A Poot, Ian Chambers

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Embryonic stem (ES) cell self-renewal efficiency is determined by the Nanog protein level. However, the protein partners of Nanog that function to direct self-renewal are unclear. Here, we identify a Nanog interactome of over 130 proteins including transcription factors, chromatin modifying complexes, phosphorylation and ubiquitination enzymes, basal transcriptional machinery members, and RNA processing factors. Sox2 was identified as a robust interacting partner of Nanog. The purified Nanog-Sox2 complex identified a DNA recognition sequence present in multiple overlapping Nanog/Sox2 ChIP-Seq data sets. The Nanog tryptophan repeat region is necessary and sufficient for interaction with Sox2, with tryptophan residues required. In Sox2, tyrosine to alanine mutations within a triple-repeat motif (S X T/S Y) abrogates the Nanog-Sox2 interaction, alters expression of genes associated with the Nanog-Sox2 cognate sequence, and reduces the ability of Sox2 to rescue ES cell differentiation induced by endogenous Sox2 deletion. Substitution of the tyrosines with phenylalanine rescues both the Sox2-Nanog interaction and efficient self-renewal. These results suggest that aromatic stacking of Nanog tryptophans and Sox2 tyrosines mediates an interaction central to ES cell self-renewal.
Original languageEnglish
Pages (from-to)2231-47
Number of pages17
JournalEMBO Journal
Issue number16
Publication statusPublished - 14 Aug 2013


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