JMJD3 acts in tandem with KLF4 to facilitate reprogramming to pluripotency
| العنوان: | JMJD3 acts in tandem with KLF4 to facilitate reprogramming to pluripotency |
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| المؤلفون: | Yujia Tang, Zhongzhou Yang, Fei Gao, Xue Wen, Yinghua Huang, Jiekai Chen, Vikas Malik, Xiaofen Huang, Miguel A. Esteban, Andrew P. Hutchins, Lulu Wang, Giacomo Volpe, Isaac A. Babarinde, Guanyu Ji, Chuanqing Tang, Hui Zhang, Carl Ward, Xichen Bao, Liangxue Lai, Lin Guo, Giuseppe Testa, Baohua Liu, Tanveer Ahmed, Shizuo Akira, Yingying Li, Duanqing Pei, Baoming Qin, Meifang Pan, Jianbin Su, Ji-Fan Hu, Xinyu Wu, Xueting Xu, Hui Zheng, Takashi Satoh, Yiwei Lai, Ralf Jauch, Runxia Lin, Li Sun, Guangjin Pan, Xiaogan Qin, Jinlong Chen |
| المصدر: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Jumonji Domain-Containing Histone Demethylases, General Physics and Astronomy, Histones, Mice, 0302 clinical medicine, Histone post-translational modifications, lcsh:Science, Promoter Regions, Genetic, Cellular Senescence, Regulation of gene expression, Multidisciplinary, Genome, Gene Expression Regulation, Developmental, Cellular Reprogramming, humanities, Chromatin, Cell biology, Enhancer Elements, Genetic, KLF4, embryonic structures, Epigenetics, biological phenomena, cell phenomena, and immunity, Reprogramming, Pluripotent Stem Cells, Transcriptional Activation, Science, Kruppel-Like Transcription Factors, Biology, Models, Biological, Chromatin structure, General Biochemistry, Genetics and Molecular Biology, Catalysis, Article, 03 medical and health sciences, Kruppel-Like Factor 4, SOX2, Animals, Cell Proliferation, Cohesin loading, Lysine, Epithelial Cells, General Chemistry, Fibroblasts, Demethylation, Gene regulation, 030104 developmental biology, biology.protein, Demethylase, lcsh:Q, 030217 neurology & neurosurgery |
| الوصف: | The interplay between the Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) and transcriptional/epigenetic co-regulators in somatic cell reprogramming is incompletely understood. Here, we demonstrate that the histone H3 lysine 27 trimethylation (H3K27me3) demethylase JMJD3 plays conflicting roles in mouse reprogramming. On one side, JMJD3 induces the pro-senescence factor Ink4a and degrades the pluripotency regulator PHF20 in a reprogramming factor-independent manner. On the other side, JMJD3 is specifically recruited by KLF4 to reduce H3K27me3 at both enhancers and promoters of epithelial and pluripotency genes. JMJD3 also promotes enhancer-promoter looping through the cohesin loading factor NIPBL and ultimately transcriptional elongation. This competition of forces can be shifted towards improved reprogramming by using early passage fibroblasts or boosting JMJD3’s catalytic activity with vitamin C. Our work, thus, establishes a multifaceted role for JMJD3, placing it as a key partner of KLF4 and a scaffold that assists chromatin interactions and activates gene transcription. Previous work suggested that histone demethylase JMJD3 is detrimental to somatic cell reprogramming. Here, the authors show that while JMJD3 has a context-independent detrimental effect on early stages of reprogramming, during late stages it activates epithelial and pluripotency genes together with Klf4. |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b1ce28b18192adb32089c843f7075da5Test https://pubmed.ncbi.nlm.nih.gov/33033262Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b1ce28b18192adb32089c843f7075da5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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