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

Gagliardi, A., Mullin, N., Ying Tan, Z., Colby, D., Kousa, A., Halbritter, F., et al. (2013). A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal. EMBO JOURNAL, 32(16), 2231-2247 [10.1038/emboj.2013.161].

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

FAVARO, REBECCA;NICOLIS, SILVIA KIRSTEN;
2013

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
Articolo in rivista - Articolo scientifico
Sox2, stem cells, transcription factors
English
2013
32
16
2231
2247
none
Gagliardi, A., Mullin, N., Ying Tan, Z., Colby, D., Kousa, A., Halbritter, F., et al. (2013). A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal. EMBO JOURNAL, 32(16), 2231-2247 [10.1038/emboj.2013.161].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/46210
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