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Title: Conversion of Sox17 into a pluripotency reprogramming factor by reengineering its association with Oct4 on DNA
Authors: Jauch, R.
Aksoy, I.
Hutchins, A.P.
Ng, C.K.L.
Tian, X.F.
Chen, J.
Palasingam, P.
Robson, P.
Stanton, L.W.
Kolatkar, P.R. 
Keywords: Endoderm differentiation
Induced pluripotent stem cells
Sox transcription factors
Issue Date: Jun-2011
Citation: Jauch, R., Aksoy, I., Hutchins, A.P., Ng, C.K.L., Tian, X.F., Chen, J., Palasingam, P., Robson, P., Stanton, L.W., Kolatkar, P.R. (2011-06). Conversion of Sox17 into a pluripotency reprogramming factor by reengineering its association with Oct4 on DNA. Stem Cells 29 (6) : 940-951. ScholarBank@NUS Repository.
Abstract: Very few proteins are capable to induce pluripotent stem (iPS) cells and their biochemical uniqueness remains unexplained. For example, Sox2 cooperates with other transcription factors to generate iPS cells, but Sox17, despite binding to similar DNA sequences, cannot. Here, we show that Sox2 and Sox17 exhibit inverse heterodimerization preferences with Oct4 on the canonical versus a newly identified compressed sox/oct motif. We can swap the cooperativity profiles of Sox2 and Sox17 by exchanging single amino acids at the Oct4 interaction interface resulting in Sox2KE and Sox17EK proteins. The reengineered Sox17EK now promotes reprogramming of somatic cells to iPS, whereas Sox2KE has lost this potential. Consistently, when Sox2KE is overexpressed in embryonic stem cells it forces endoderm differentiation similar to wild-type Sox17. Together, we demonstrate that strategic point mutations that facilitate Sox/Oct4 dimer formation on variant DNA motifs lead to a dramatic swap of the bioactivities of Sox2 and Sox17. © AlphaMed Press.
Source Title: Stem Cells
ISSN: 10665099
DOI: 10.1002/stem.639
Appears in Collections:Staff Publications

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