Please use this identifier to cite or link to this item: https://doi.org/10.1002/stem.639
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
Pluripotency
Reprogramming
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. https://doi.org/10.1002/stem.639
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
URI: http://scholarbank.nus.edu.sg/handle/10635/113181
ISSN: 10665099
DOI: 10.1002/stem.639
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

58
checked on Jul 14, 2018

WEB OF SCIENCETM
Citations

53
checked on Jun 19, 2018

Page view(s)

72
checked on Jul 6, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.