JMJD3 acts in tandem with KLF4 to facilitate reprogramming to pluripotency

Huang，Yinghua1,2; Zhang，Hui3; Wang，Lulu1,2; Tang，Chuanqing1,2; Qin，Xiaogan1,2; Wu，Xinyu1,2,4; Pan，Meifang1,2,4; Tang，Yujia1,2; Yang，Zhongzhou1; Babarinde，Isaac A.5; Lin，Runxia1,2,4; Ji，Guanyu6; Lai，Yiwei1,7; Xu，Xueting1,2,8; Su，Jianbin1,2; Wen，Xue9; Satoh，Takashi10; Ahmed，Tanveer1,2; Malik，Vikas1,7; Ward，Carl1,7; Volpe，Giacomo1,7; Guo，Lin1; Chen，Jinlong1; Sun，Li5; Li，Yingying3; Huang，Xiaofen1; Bao，Xichen1,3,11; Gao，Fei6,12; Liu，Baohua13; Zheng，Hui1,3,11; Jauch，Ralf14; Lai，Liangxue1,3,11; Pan，Guangjin1,3,11; Chen，Jiekai1,3,11; Testa，Giuseppe15; Akira，Shizuo10; Hu，Jifan9; Pei，Duanqing1,3; Hutchins，Andrew P.5; Esteban，Miguel A.1,7,11,16; Qin，Baoming1,2,3,11

2020-12-01

10.1038/s41467-020-18900-z

Nature Communications   影响因子和分区

2041-1723

2041-1723

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.

SCI

英语

NI论文

其他

National Key Research and Development Program of China[2016YFA0100300][2016YFA0100102][2018YFA0106903][2018YFA0106902] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16030502] ; National Natural Science Foundation of China[31671537][31970589][31950410553][31850410486][31771454] ; Innovative Team Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory[2018GZR110103001] ; Guangdong Province Science and Technology Program[2015A030308007][2016B030229007][2017B050506007][2019A050510004] ; Guangzhou Science and Technology Program[201907010039][201807010066] ; Shenzhen Municipal Commission of Science and Technology Innovation[ZDSYS20190902093401689][JCYJ20180507182044945] ; Science and Technology Planning Project of Guangdong Province, China[2017B030314056] ; Guangdong Special Support Program[2016TX03R366] ; Chinese Academy of Sciences President's International Fellowship Initiative for Postdoctoral Researchers[2019PB0177] ; Chinese Academy of Sciences President's International Fellowship for Foreign Experts[2020FSB0002]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000581917700002

NATURE RESEARCH

2-s2.0-85092137317

Scopus

1.Chinese Academy of Sciences (CAS) Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine,Guangzhou Institutes of Biomedicine and Health (GIBH),CAS,Guangzhou,510530,China
2.Laboratory of Metabolism and Cell Fate,GIBH,CAS,Guangzhou,510530,China
3.Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory),Guangzhou,510005,China
4.University of Chinese Academy of Sciences,Beijing,100049,China
5.Department of Biology,Southern University of Science and Technology,Shenzhen,518055,China
6.Science and Technology Department,E-GENE,Shenzhen,518118,China
7.Laboratory of Integrative Biology,GIBH,CAS,Guangzhou,510530,China
8.School of Life Sciences,University of Science and Technology of China,Hefei,230027,China
9.Stem Cell and Cancer Center,First Affiliated Hospital,Jilin University,Changchun,130061,China
10.Department of Host Defense,Research Institute for Microbial Diseases,Osaka University,Osaka,565-0871,Japan
11.Joint School of Life Sciences,GIBH and Guangzhou Medical University,Guangzhou,511436,China
12.Agricultural Genomics Institute at Shenzhen,Chinese Academy of Agricultural Sciences,Shenzhen,518120,China
13.Health Science Center,Shenzhen University,Shenzhen,518060,China
14.School of Biomedical Sciences,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong
15.Department of Experimental Oncology,European Institute of Oncology,Milan,20139,Italy
16.Institute for Stem Cells and Regeneration,CAS,Beijing,100101,China

Huang，Yinghua,Zhang，Hui,Wang，Lulu,et al. JMJD3 acts in tandem with KLF4 to facilitate reprogramming to pluripotency[J]. Nature Communications,2020,11(1).

Huang，Yinghua.,Zhang，Hui.,Wang，Lulu.,Tang，Chuanqing.,Qin，Xiaogan.,...&Qin，Baoming.(2020).JMJD3 acts in tandem with KLF4 to facilitate reprogramming to pluripotency.Nature Communications,11(1).

Huang，Yinghua,et al."JMJD3 acts in tandem with KLF4 to facilitate reprogramming to pluripotency".Nature Communications 11.1(2020).