Yubo Zhang课题组

Yubo Zhang课题组

　　Yubo  Zhang  Lab

　　首席科学家/课题组长介绍：

　　Yubo Zhang，研究员，博士生导师，动物功能基因组学创新团队首席科学家。入选中国农科院“青年英才”。主要研究领域为动物三维基因组学；长期专注于三维基因组技术研发、三维基因转录调控网络构建及非编码DNA调控元件对基因转录调控过程的研究。在Nature、Genome Research、PNAS等国际学术期刊上发表近20篇学术论文，累计他引超900次

　　Zhang Yubo, Principle Investigator, Doctoral Advisor, the chief scientist of the Animal Functional Genomics Innovation Group. His main research fields are animal three-dimensional genomics, three-dimensional genomics technology development, construction of three-dimensional gene transcription regulatory network and research on the process of gene transcription regulation by non-coding DNA regulatory elements. His researches have been published on high profile journals including Nature and PNAS with more than 900 citations. In 2017, he was awardee of the national “The Thousand Talents Plan, Youth”. In 2015, he was awarded the "Young Talents" by Chinese Academy of Agricultural Sciences.

　　

　　研究成果：

　　论著：

　　1. Peng YL, Zhang YB. Enhancer and super-enhancer: Positive regulators in gene transcription. Animal Model Exp Med. 2018; https://doi.org/10.1002/ame2.12032 (通讯作者) 

　　2. Yubo Zhang. 三维基因组学与精准生物学[J]. 中国生物化学与分子生物学报, 2018, 34(4): 351-363. (通讯作者)

　　3. Kamada R, Yang W, Zhang Y, Patel MC, Yang Y, Ouda R, Dey A, Wakabayashi Y, Sakaguchi K, Fujita T, Tamura T, Zhu J, Ozato K., Interferon stimulation creates chromatin marks and establishes transcriptional memory. Proc Natl Acad Sci., 2018, doi: 10.1073/pnas.1720930115. (共同一作)

　　4. Yubo Zhang. 三维基因组学与精准生物学[J]. 中国生物化学与分子生物学报, 2018(4).

　　5. Kong S , Zhang Y . Deciphering Hi-C: from 3D genome to function[J]. Cell Biology and Toxicology, 2019, 35(1):15-32.

　　6. Yubo Zhang, Chee Hong Wong, Ramon Birnbaum, Guoliang Li, Rebecca Favaro, Chew Yee Nyan, Eunice Tai, Joanne Lim Hui Ping, Huay Mei Poh, Fabianus Hendriyan Mulawadi, Silvia Nicolis, Nadav Ahituv, Yijun Ruan and Chia-Lin Wei. Dynamic chromatin connectivity maps reveal lineage specific regulation. Nature. 2013, 504, 306-310.

　　7. Siyuan Kong, Li Li, Wenjuan Zhu, Leilei Xin, Jinxue Ruan, Yubo Zhang, Shulin Yang, and Kui Li. Genetic characteristics of polycistronic system-mediated randomly-inserted multi-transgenes in miniature pigs and mice:[J]. Molecular Medicine Reports, 2018, 17(1):37-50.

　　8. Kong, S., Ruan, J., Zhang, K., Hu, B., Cheng, Y., & Zhang, Y., et al. (2018). Kill two birds with one stone: making multi-transgenic pre-diabetes mouse models through insulin resistance and pancreatic apoptosis pathogenesis. Peerj, 6(5), e4542.

　　专利：

　　1.201610995880.X，一种高效的全基因组染色质构象技术eHi-C，Yubo Zhang，孔思远，黄其通，黄雷，王秋雁，白立景，张高林，钟学优；

　　2. 201710773996.3，一种基于少量细胞全基因组染色质高分辨率构象技术eHi-C 2.0，Yubo Zhang，孔思远，黄其通，李琳，黄雷，白立景，彭艳玲

　　3. 201810589919.7，一种消除三维基因组学技术噪音的方法及应用，Yubo Zhang，孔思远，张高林，范磊，黄其通，李清，黄雷，彭艳玲；.

　　4. 201810589904，利用外切酶组合消除三维基因组学技术噪音的方法及应用, Yubo Zhang，孔思远，张高林，黄其通，范磊，李清，黄雷，彭艳玲；

　　5. 201811546406.4，一种精准获得全基因组范围内结构变异方法，Yubo Zhang，付亚娟，徐波，王帅。

　　

　　团队研究方向: 

　　本团队紧紧围绕三维基因组学在动物精准育种中的应用这一科学问题开展工作，主要研究方向包括：（1）三维基因组学技术研发。以实践精准生物学为导向，研发可靠、高效的三维基因组学技术；（2）三维基因组学相关生物信息学新算法研发及应用。进行生物信息学新算法的研发，及现存算法的优化、标准化及程式化研究；（3）动物早期发育过程中三维转录调控网络研究。整合多组学数据，阐明关键转录因子或调控元件的生物学效应，揭示动物早期发育过程相关的重大科学问题。

　　We focus our research on 3D genomics and precise animal breeding. The main research directions are as follows. Firstly, reliable and efficient 3D genomics technology is developed to investigate the biological effects of genes, regulatory elements and their long-distance interactions. Secondly, new algorithms are developed and applied for analyzing 3D genomics data. The goal is to optimize, standardize and program existing algorithms. Thirdly, 3D transcriptional regulation network is studied in early development of mice. By constructing a dynamic three-dimensional transcriptional regulatory network and integrating multiple sets of data, we hope to clarify the biological effects of key transcription factors or regulatory elements, thus revealing important scientific issues related to animal early development.

 

　　研究进展：

　　1）快速、高效的增强子元件编辑技术为ESC增强子功能研究提供了平台。

　　Sox2 基因的增强子活性分析：E1 和 E3 在 mESCs 细胞中表现为明显的增强子活性，而 E2 的增强子活性微弱。利用CRISPR/Cas9系统在 mESCs 细胞中构建三个增强子敲除的细胞系，相比于野生型，敲除细胞的Sox2 基因表达水平显著下降。

　　Fast and efficient editing technology of enhancers provides a platform for the research of ESC enhancer functions.

　　Enhancer activity analysis of Sox2 gene: E1 and E3 showed obvious enhancer activity in mESCs cells, while the enhancer activity of E2 was weak . Three enhancer knockout cell lines were constructed using CRISPR/Cas9 system in mESCs cells. Compared with wild type, the expression level of Sox 2 gene in knockout cells decreased significantly .

　　2）改良并研发了eHi-C技术

　　针对原有Hi-C技术假阳性率较高及背景噪音较高等缺点，团队在Hi-C技术中成功引入“条码”策略，显著降低了原技术中假阳性率，为深入开展三维/多维基因组学研究提供了技术支撑。

　　eHi-C technologies have been improved and developed.

　　In view of the high false positive rate and high background noise of the original Hi-C technology, the team successfully introduced the "bar code" strategy in Hi-C technology, which significantly reduced the false positive rate in the original technology , providing technical support for the further development of three-dimensional/multi-dimensional genomics research.

　　3）改进优化了染色质环的识别技术

　　在基于统计分析交互片段区域的显著性的基础上，引入基于局部密度聚类分析方法，并开发相应程序。相较提高现有的识别方法，可提高计算效率，可以基于Hi-C数据高效识别染色质环，为动物及猪的三维/多维基因组学信息提取及转录调控研究提供高效工具。

　　Improvement and optimization of chromatin ring recognition technology

　　Based on the significant interaction region of statistical analysis, we introduced a local density clustering analysis method and developed the corresponding program. Compared with the existing methods, the new discriminating algorithm improves the computational efficiency and accurately identifies the chromatin loops based on Hi-C data which provides an efficient tool for 3D / multidimensional genomics information mining and transcriptional regulation studies in animals and pigs.

 

Yubo Zhang课题组更新于2020年7月