Research Areas

DNA replication is the basis for the accurate transmission of genetic information, which is jointly regulated by genetic and epigenetic factors. In the genome, DNA replication starts from certain special regions called "replication origins". Correct initiation of DNA replication is the basis for cell growth, division, and physiological function. However, incorrect initiation of DNA replication, either in location or time, can lead to mutations in DNA sequences, genomic instability, and even errors in the transmission of genetic information, which can promote the development of cancer and genetic diseases. Therefore, the research direction of our team is to investigate the epigenetic regulatory mechanisms of DNA replication and their roles in tumor development and cell differentiation and development.

Highlights

Dr.Haizhen Long has conducted a series of studies on the biological functions of epigenetic factors in the DNA replication and transcription processes. The research results have been published in journals such as Nature, Nature Structural & Molecular Biology, BMC Biology, Genes & Development, and Genome Biology. The research published by Nature was awarded one of the Top 10 Scientific Advances in China in 2020 (Advance 4: Revealing the Key Steps of Human Genetic Material Transmission) and was selected as a representative achievement in the "Thirteenth Five-Year Plan" by the Ministry of Science and Technology. Dr.Haizhen Long has also received support from various projects such as Shenzhen Outstanding Youth, China Association for Science and Technology Youth Talent Support Program, the Ministry of Science and Technology of China, National Natural Science Foundation of China, and Youth Innovation Promotion Association of Chinese Academy of Sciences.

Major research are as follows:

(1) The mechanism for recognizing DNA replication origins in multicellular eukaryotes is still unclear. We have revealed a novel epigenetic regulatory pathway for DNA replication mediated by the histone variant H2A.Z - SUV420H1 - H4K20me2 - ORC1. This research was published in the journal Nature, received F1000 prime recommendation, and was awarded one of the Top 10 Scientific Advances in China in 2020 (Advance 4: Revealing the Key Steps of Human Genetic Material Transmission) and was exhibited in the National "Thirteenth Five-Year Plan" Science and Technology Innovation Achievement Exhibition. Then we collaborated with scientists in structural biology and chemistry to further explore the translational application prospects of this pathway.

The role of H2A.Z on DNA replication initiation

(2) We found that the O-GlcNAc modification of histone H4S47 can promote the recruitment of DDK on chromatin, helping the helicase MCM complex to complete activation and initiate DNA replication. This study connects DNA replication with cell metabolism, opening up new perspectives for a deeper understanding of how cells ensure the correct transmission of genetic material under dynamically changing nutritional environments. This research was published in the journal Nature Structural & Molecular Biology.

(3) Replication, transcription, and translation are the core contents of the central dogma. We have studied the role of epigenetics in gene transcription regulation and found that histone variants H2A.Z and H3.3 can co-regulate the dynamic changes in chromatin higher-order structure, thereby regulating gene transcription and participating in important physiological processes such as immunity.

Honors

• 2023 Shenzhen Outstanding Science and Technology Innovation Talent Training Program (Outstanding Youth Program) 

• 2022 Selected for the 7th "Youth Talent Support Program" of the China Association for Science and Technology Life Science Society 

• 2020 Member of the Youth Innovation Promotion Association of Chinese Academy of Sciences

Related News

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Selected Publications

(1) Haizhen Long#; Liwei Zhang#; Mengjie Lv#; Zengqi wen#; Wenhao Zhang; Xiulan Chen; Peitao Zhang; Tongqing Li; Luyuan Chang; Caiwei Jin; Guozhao Wu; Xi Wang; Fuquan Yang; Jianfeng Pei; Ping Chen; Raphael Margueron; Haiteng Deng; Mingzhao Zhu*; Guohong Li*; H2A.Z facilitates licensing and activation of early replication origins, Nature, 2020, 577(7791):576-581

(2) Li Huang#; Youwang Wang#; Haizhen Long#*; Haoqiang Zhu; Zengqi Wen; Liwei Zhang; Wenhao Zhang; Zhenqian Guo; Longge Wang; Fangyi Tang; Jie Hu; Keyan Bao; Ping Zhu*; Guohong Li*; Zheng Zhou*; Structural insight into H4K20 methylation on H2A.Z-nucleosome by SUV420H1, Molecular Cell, 2023, 83(16): 2884-2895

(3) Yingying Zou#; Jiayao Pei#; Haizhen Long#; Liting Lan; Kejian Dong; Tingting Wang; Ming Li; Zhexuan Zhao; Lirun Zhu; Gangxuan Zhang; Xin Jin; Yang Wang; Zengqi Wen; Min Wei; Yunpeng Feng*; H4S47 O-GlcNAcylation regulates the activation of mammalian replication origins, Nature Structural & Molecular Biology, 2023 Jun;30(6):800-811.

(3) Yan Wang#; Haizhen Long#; Juan yu#; Liping Dong#; Michel Wassef; Baowen Zhuo; Xia Li; Jicheng Zhao; Min Wang; Cuifang Liu; Zengqi Wen; Luyuan Chang; Ping Chen; Qian-fei Wang; Xueqing Xu; Raphael Margueron*; Guohong Li*; Histone variants H2A.Z and H3.3 coordinately regulate PRC2-dependent H3K27me3 deposition and gene expression regulation in mES cells, BMC Biology, 2018, 16(107).

(4) Liuxin Shi; Li Huang; Haizhen Long; Aoqun Song; Zheng zhou*; Structural basis of nucleosomal H4K20 methylation by methyltransferase SET8, FASEB 2022 Jun;36(6)

(5) Ping Chen#, Jicheng Zhao#, Yan Wang#, Min Wang, Haizhen Long, Dan Liang, Li Huang, Zengqi Wen, Wei Li, Xia Li, Hongli Feng, Haiyong Zhao, Ping Zhu, Ming Li, Qian-fei Wang, Guohong Li (2013). "H3.3 actively marks enhancers and primes gene transcription via opening higher-ordered chromatin." Genes Dev. 27, 2109-2124 (2013)

(6) Yongzheng Li#, Boxin Xue#, Mengling Zhang#, Liwei Zhang, Yingping Hou, Yizhi Qin, Haizhen Long, Qian Peter Su, Yao Wang, Xiaodong Guan, Yanyan Jin, Yuan Cao, Guohong Li, Yujie Sun, “Transcription-coupled structural dynamics of topologically associating domains regulate replication origin efficiency”, Genome Biol.2021;22:206