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Abstract
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 language | English |
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Pages (from-to) | 2231-47 |
Number of pages | 17 |
Journal | EMBO Journal |
Volume | 32 |
Issue number | 16 |
DOIs | |
Publication status | Published - 14 Aug 2013 |
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Dive into the research topics of 'A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal'. Together they form a unique fingerprint.Projects
- 1 Finished
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Transcription factor dynamics in control of pluripotent cell function and identity
1/06/11 → 31/05/14
Project: Research