Pluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2
| العنوان: | Pluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2 |
|---|---|
| المؤلفون: | Zahir Shah, Sebastian Pott, Dennis Zimmer, Vikas Malik, Veeramohan Veerapandian, Miguel A. Esteban, Sergiy Velychko, Markus Holzner, Marius Arend, Mingxi Weng, Sebastiaan H. Meijsing, Yogesh Srivastava, Ralf Jauch, Laura V. Glaser, Yanpu Chen, Andrew P. Hutchins, Huating Wang, Jiekai Chen, Hans R. Schöler |
| المصدر: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-16 (2019) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Time Factors, cells, General Physics and Astronomy, Stem cells, 02 engineering and technology, medicine.disease_cause, Gene regulatory networks, lcsh:Science, Cells, Cultured, reproductive and urinary physiology, Mutation, Multidisciplinary, Cellular Reprogramming, 021001 nanoscience & nanotechnology, Chromatin, Cell biology, KLF4, embryonic structures, biological phenomena, cell phenomena, and immunity, 0210 nano-technology, Reprogramming, Epithelial-Mesenchymal Transition, Science, Induced Pluripotent Stem Cells, Primary Cell Culture, Mice, Transgenic, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Kruppel-Like Factor 4, 03 medical and health sciences, stomatognathic system, SOX2, medicine, Animals, Gene silencing, Enhancer, POU domain, SOXB1 Transcription Factors, fungi, General Chemistry, Fibroblasts, Embryo, Mammalian, 030104 developmental biology, Octamer Transcription Factor-6, lcsh:Q, sense organs, Protein Multimerization, Octamer Transcription Factor-3 |
| الوصف: | Oct4, along with Sox2 and Klf4 (SK), can induce pluripotency but structurally similar factors like Oct6 cannot. To decode why Oct4 has this unique ability, we compare Oct4-binding, accessibility patterns and transcriptional waves with Oct6 and an Oct4 mutant defective in the dimerization with Sox2 (Oct4defSox2). We find that initial silencing of the somatic program proceeds indistinguishably with or without Oct4. Oct6 mitigates the mesenchymal-to-epithelial transition and derails reprogramming. These effects are a consequence of differences in genome-wide binding, as the early binding profile of Oct4defSox2 resembles Oct4, whilst Oct6 does not bind pluripotency enhancers. Nevertheless, in the Oct6-SK condition many otherwise Oct4-bound locations become accessible but chromatin opening is compromised when Oct4defSox2 occupies these sites. We find that Sox2 predominantly facilitates chromatin opening, whilst Oct4 serves an accessory role. Formation of Oct4/Sox2 heterodimers is essential for pluripotency establishment; however, reliance on Oct4/Sox2 heterodimers declines during pluripotency maintenance. Oct4, along with Sox2 and Klf4 can induce pluripotency, but structurally similar factors like Oct6 cannot. Here, using pluripotency competent and incompetent factors, the authors show that Sox2 plays a dominant role in facilitating chromatin opening at Oct4 bound DNA early during reprogramming to pluripotency. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::95564dd529158482eb3683b451d2c99dTest https://hdl.handle.net/21.11116/0000-0005-9084-221.11116/0000-0005-9086-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....95564dd529158482eb3683b451d2c99d |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |