A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal.
EMBO J
; 32(16): 2231-47, 2013 Aug 14.
Article
in En
| MEDLINE
| ID: mdl-23892456
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.
Full text:
1
Database:
MEDLINE
Main subject:
Homeodomain Proteins
/
Cell Proliferation
/
Embryonic Stem Cells
/
Protein Interaction Domains and Motifs
/
SOXB1 Transcription Factors
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
EMBO J
Year:
2013
Type:
Article
Affiliation country:
United kingdom