Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm
How regulatory information is encoded in the genome is poorly understood and poses a challenge when studying biological processes. We demonstrate here that genomic redistribution of Oct4 by alternative partnering with Sox2 and Sox17 is a fundamental regulatory event of endodermal specification. We s...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
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2015
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| Online Access: | https://hdl.handle.net/10356/106625 http://hdl.handle.net/10220/25036 |
| _version_ | 1824454839971610624 |
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| author | Ng, Calista Keow Leng Herath, Wishva Lili, Sun Hutchins, Andrew P Robson, Paul Kolatkar, Prasanna R Stanton, Lawrence W Aksoy, Irene Jauch, Ralf Chen, Jiaxuan Dyla, Mateusz Divakar, Ushashree Bogu, Gireesh K Teo, Roy |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Ng, Calista Keow Leng Herath, Wishva Lili, Sun Hutchins, Andrew P Robson, Paul Kolatkar, Prasanna R Stanton, Lawrence W Aksoy, Irene Jauch, Ralf Chen, Jiaxuan Dyla, Mateusz Divakar, Ushashree Bogu, Gireesh K Teo, Roy |
| author_sort | Ng, Calista Keow Leng |
| collection | NTU |
| description | How regulatory information is encoded in the genome is poorly understood and poses a challenge when studying biological processes. We demonstrate here that genomic redistribution of Oct4 by alternative partnering with Sox2 and Sox17 is a fundamental regulatory event of endodermal specification. We show that Sox17 partners with Oct4 and binds to a unique ‘compressed’ Sox/Oct motif that earmarks endodermal genes. This is in contrast to the pluripotent state where Oct4 selectively partners with Sox2 at ‘canonical’ binding sites. The distinct selection of binding sites by alternative Sox/Oct partnering is underscored by our demonstration that rationally point‐mutated Sox17 partners with Oct4 on pluripotency genes earmarked by the canonical Sox/Oct motif. In an endodermal differentiation assay, we demonstrate that the compressed motif is required for proper expression of endodermal genes. Evidently, Oct4 drives alternative developmental programs by switching Sox partners that affects enhancer selection, leading to either an endodermal or pluripotent cell fate. This work provides insights in understanding cell fate transcriptional regulation by highlighting the direct link between the DNA sequence of an enhancer and a developmental outcome. |
| first_indexed | 2025-02-19T03:28:42Z |
| format | Journal Article |
| id | ntu-10356/106625 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:28:42Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/1066252023-02-28T17:03:11Z Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm Ng, Calista Keow Leng Herath, Wishva Lili, Sun Hutchins, Andrew P Robson, Paul Kolatkar, Prasanna R Stanton, Lawrence W Aksoy, Irene Jauch, Ralf Chen, Jiaxuan Dyla, Mateusz Divakar, Ushashree Bogu, Gireesh K Teo, Roy School of Biological Sciences DRNTU::Science::Biological sciences How regulatory information is encoded in the genome is poorly understood and poses a challenge when studying biological processes. We demonstrate here that genomic redistribution of Oct4 by alternative partnering with Sox2 and Sox17 is a fundamental regulatory event of endodermal specification. We show that Sox17 partners with Oct4 and binds to a unique ‘compressed’ Sox/Oct motif that earmarks endodermal genes. This is in contrast to the pluripotent state where Oct4 selectively partners with Sox2 at ‘canonical’ binding sites. The distinct selection of binding sites by alternative Sox/Oct partnering is underscored by our demonstration that rationally point‐mutated Sox17 partners with Oct4 on pluripotency genes earmarked by the canonical Sox/Oct motif. In an endodermal differentiation assay, we demonstrate that the compressed motif is required for proper expression of endodermal genes. Evidently, Oct4 drives alternative developmental programs by switching Sox partners that affects enhancer selection, leading to either an endodermal or pluripotent cell fate. This work provides insights in understanding cell fate transcriptional regulation by highlighting the direct link between the DNA sequence of an enhancer and a developmental outcome. Published version 2015-02-12T05:05:59Z 2019-12-06T22:15:08Z 2015-02-12T05:05:59Z 2019-12-06T22:15:08Z 2013 2013 Journal Article Aksoy, I., Jauch, R., Chen, J., Dyla, M., Divakar, U., Bogu, G. K., & et al. (2013). Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm. The EMBO journal, 32(7), 938-953. 0261-4189 https://hdl.handle.net/10356/106625 http://hdl.handle.net/10220/25036 10.1038/emboj.2013.31 23474895 en The EMBO journal © 2013 European Molecular Biology Organization. This paper was published in The EMBO Journal and is made available as an electronic reprint (preprint) with permission of European Molecular Biology Organization. The paper can be found at the following official DOI: [http://dx.doi.org/10.1038/emboj.2013.31]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Ng, Calista Keow Leng Herath, Wishva Lili, Sun Hutchins, Andrew P Robson, Paul Kolatkar, Prasanna R Stanton, Lawrence W Aksoy, Irene Jauch, Ralf Chen, Jiaxuan Dyla, Mateusz Divakar, Ushashree Bogu, Gireesh K Teo, Roy Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm |
| title | Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm |
| title_full | Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm |
| title_fullStr | Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm |
| title_full_unstemmed | Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm |
| title_short | Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm |
| title_sort | oct4 switches partnering from sox2 to sox17 to reinterpret the enhancer code and specify endoderm |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/106625 http://hdl.handle.net/10220/25036 |
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