Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
Epigenetics; DNA methylation; DNA methyltransferases (Dnmt); DNA demethylases;Tet enzymes; Leukemogenesis; Gametogenesis.
Most biological activities have an epigenetic basis. A given cell has its own epigenetic setup which allows for various biochemical events to proceed. Our major research effort is focused on gene regulation mechanisms involving DNA methylation. The key players in DNA methylation are DNA methyltransferases (DNMTs) and DNA dioxygenases commonly known as TET enzymes. Surprisingly, there are only a couple of DNMT and TET enzymes which are responsible respectively for the generation and removal of genomic methylation patterns. Both DNMT and TET enzymes are essential for early development in mammals. They regulate crucial fate-determining genes involved in stem cell maintenance, lineage commitment etc. These DNA-modifying enzymes can therefore be regarded as ¡°regulators of regulators¡± in development. Though the importance of DNA modifications has long been recognized in the epigenetics field, advance in the understanding of biochemical mechanisms has been slow in general. In addition to the major subject surrounding the mechanisms of DNA methylation and demethylation which we put most of our efforts into, we are also extending our research to other important issues such as new types of DNA modifications and contribution of aberrant epigenetic regulation to tumorigenesis.
- Hai-Qiang Dai, Bang-An Wang, Lu Yang, Jia-Jia Chen, Guo-Chun Zhu, Mei-Ling Sun, Hao Ge, Rui Wang, Deborah L. Chapman, Fuchou Tang, Xin Sun*, Guo-Liang Xu*. (2016). TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling. Nature 538, 528-532.
- Fan Guo, Xianlong Li, Dan Liang, Tong Li, Ping Zhu, Hongshan Guo, Xinglong Wu, Lu Wen, Tian-Peng Gu, Colum P.Walsh, Jinsong Li*, Fuchou Tang*, Guo-Liang Xu*.(2014). Active and Passive Demethylation of Male and Female Pronuclear DNA in the Mammalian Zygote. Cell Stem Cell 15, 477-458.
- Xiao Hu, Lei Zhang, Shi-Qing Mao, Zheng Li, Jiekai Chen, Run-Rui Zhang, Hai-Ping Wu, Juan Gao, Fan Guo, Wei Liu, Gui-Fang Xu, Hai-Qiang Dai, Yujiang Geno Shi, Xianlong Li, Boqiang Hu, Fuchou Tang, Duanqing Pei, Guo-Liang Xu. (2014). Tet and TDG Mediate DNA Demethylation Essential for Mesenchymal-to-Epithelial Transition in Somatic Cell Reprogramming. Cell Stem Cell 14,512-522.
- Run-Rui Zhang, Qing-Yan Cui, Kiyohito Murai, Yen Ching Lim, Zachary D. Smith, Shengnan Jin, Peng Ye, Luis Rosa, Yew Kok Lee, Hai-Ping Wu, Wei Liu, Zhi-Mei Xu, Lu Yang, Yu-Qiang Ding, Fuchou Tang, Alexander Meissner, Chunming Ding*, Yanhong Shi*, Guo-Liang Xu*. (2013) Tet1 Regulates Adult Hippocampal Neurogenesis and Cognition. Cell Stem Cell 13, 237-245.
- Jiekai Chen, Lin Guo, Lei Zhang, Haoyu Wu, Jiaqi Yang, He Liu, Xiaoshan Wang, Xiao Hu, Tianpeng Gu, Zhiwei Zhou, Jing Liu, Jiadong Liu, Hongling Wu, Shi-Qing Mao, Kunlun Mo, Yingying Li, Keyu Lai, Jing Qi, Hongjie Yao, Guangjin Pan, Guo-Liang Xu*, Duanqing Pei*. (2013). Vitamin C modulates Tet1 function during somatic cell reprogramming. Nature Genetics, 45,1504-1509.
- Hui Yang, Linyu Shi, Bang-An Wang, Dan Liang, Cuiqing Zhong, Wei Liu, Yongzhan Nie, Jie Liu, Jing Zhao, Xiang Gao, Dangsheng Li, Guo-Liang Xu*, Jinsong Li*. (2012) Generation of Genetically Modified Mice by Oocyte Injection of Androgenetic Haploid Embryonic Stem Cells. Cell. 149,605-617.
- Yu-Fei He, Bin-Zhong Li, Zheng Li, Peng Liu, Yang Wang, Qingyu Tang, Jianping Ding, Yingying Jia, Zhangcheng Chen, Lin Li, Yan Sun, Xiuxue Li, Qing Dai, Chun-Xiao Song, Kangling Zhang, Chuan He, Guo-Liang Xu. (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science, 333, 1303-07.
- Tian-Peng Gu, Fan Guo, Hui Yang, Hai-Ping Wu, Gui-Fang Xu, Wei Liu, Zhi-Guo Xie, Linyu Shi, Xinyi He, Seung-gi Jin, Khursheed Iqbal, Yujiang Geno Shi, Zixin Deng, Piroska E. Szab¨®, Gerd P. Pfeifer, Jinsong Li* and Guo-Liang Xu*. (2011) The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature, 477,606-610.
- Jia-Lei Hu, Bo Zhou, Kang-Ling Zhang, Jin-Qiu Zhou and Guo-Liang Xu. (2009) The N-terminus of histone H3 is required for de novo DNA methylation in chromatin. PNAS 106, 22187-22192.
- Yuki O., Feng Q., Lin Y., Jiang Q., Li Y., Coffield V.M., Su L., Guo-Liang Xu* and Zhang Y*. (2005) hDOT1L Links Histone Methylation to Leukemogenesis. Cell 121,167-178.
- Bourc´his D., Guo-Liang Xu, C.-S. Lin, B. Bollman and T. H. Bestor. (2001) Dnmt3L and the establishment of maternal genomic imprints. Science 294, 2536-2539.
- Guo-Liang Xu, T. H. Bestor, D. Bourc´his, C.L. Hsieh, N. Tommerup, M., Bugge, X., Qu, J. J. Russo and E. Viegas-P¨¦quignot. (1999) Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402, 187-191.
- Guo-Liang Xu and T. H. Bestor. (1997) Cytosine methylation targeted to predetermined sequences. Nature Genetics 17, 376-378.
- Chuang, L.S.H., Ian H.-I., Hoh H.-H., Ng H.-H., Guo-Liang Xu and Li B.F.L. (1997) Human DNA-(Cytosine-5) methyltransferase ¨CPCNA complex as a target for p21 WAF1. Science 277, 1996-2000.
Education Background & Academic Experience
B.S. 1985.7 Dept of Biology, Zhejiang University, China.
M.S. 1988.7 Institute of Genetics, Chinese Academy of Sciences, Beijing;
Ph.D 1993.3 Max Planck Institute (MPI) for Molecular Genetics, Berlin, Germany
1993.5-1994.7, postdoctoral study, Otto-Warburg Laboratorium, MPI, Berlin Germany;
1994.8-1995.9, principal investigator, Biosciences Center, National University of Singapore;
1995.10-2000.4, postdoctoral study, Department of Genetics and Development, Columbia University, New York.
2000.5-2001.7, postdoctoral study, Department of Medicine, Columbia University, New York.
2001.8- present, leader of Max Planck Junior Research Group, Institute of Biochemistry and Cell Biology, CAS, Shanghai, China.