| First Author | Gagliardi A | Year | 2013 |
| Journal | EMBO J | Volume | 32 |
| Issue | 16 | Pages | 2231-47 |
| PubMed ID | 23892456 | Mgi Jnum | J:204621 |
| Mgi Id | MGI:5532893 | Doi | 10.1038/emboj.2013.161 |
| Citation | Gagliardi A, et al. (2013) A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal. EMBO J 32(16):2231-47 |
| abstractText | 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. |
