Brief intro:
- Author: Yinghua Huang, Hui Zhang, Lulu Wang, Chuanqing Tang, Xiaogan Qin, Xinyu Wu, Meifang Pan,Yujia Tang, Zhongzhou Yang, Isaac A. Babarinde, Runxia Lin, Guanyu Ji, Yiwei Lai, Xueting Xu, Jianbin Su, Xue Wen, Takashi Satoh, Tanveer Ahmed, Vikas Malik, Carl Ward, Giacomo Volpe, Lin Guo, Jinlong Chen, Li Sun, Yingying Li, Xiaofen Huang, Xichen Bao, Fei Gao, Baohua Liu, Hui Zheng, Ralf Jauch, Liangxue Lai, Guangjin Pan, Jiekai Chen, Giuseppe Testa, Shizuo Akira, Jifan Hu, Duanqing Pei, Andrew P. Hutchins, Miguel A. Esteban, and Baoming Qin
- Journal: Nat Commun
- Doi: https://www.doi.org/10.1038/s41467-020-18900-z
- Publication Date: 2020 Oct 8
Products/Services used in the paper
Quotation shows PackGene:For the reprogramming of Jmjd3 cKO MEFs, Jmjd3fl/fl MEFs at P1 were infected with Cre or control RFP adeno-associated viruses (PackGene) for 24 h to complete JMJD3 JmjC domain deletion and then these cells were reprogrammed to pluripotency colonies in standard way.
Research Field:reprogramming
Abstract
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.
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