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Journal of genetics and Genomics 2008年第7期35卷 431-439页

作者： Yu Wu Yinghua He Hongyu Zhang Xinlan Dai Xiaoyu Zhou Jun Gu Guan Wang Jingde Zhu Fudan University School of Medicine Shanghai 200032 China cancer epigenetics and gene therapy Program The State-key Laboratory for Oncogenes and Related Genes Shanghai Cancer Institute Shanghai Jiaotong University Shanghai 200032 China

Liver cancer is one of the most threatening diseases in Chinese population. Just like in other tissues, tumor initiation and development in liver involve multiple steps of genetic and epigenetic alterations with several unknown details. However, unlike in other tissues, a tissue specific inducible Cre recombinase system that allows temporal and spatial deletion of a target DNA fragment is still not available for in vivo functional gene annotation in hepatocytes. In our pursuit to establish such a mouse model, we designed a dual inducible Cre transgene system and tested it in cultured cells. By combining a CCAAT/enhancer binding protein β （C/EBP β） promoter derived Tet-off expression system and the estrogen receptor （ER） mediated functional control, we show a desirable profile of both hepatocyte-specificity and regulability of the Cre expression in a series of critical assessments in the cell culture system, which provides confidence in continuation of our ongoing pursuit in mouse.

关键词： Cre/loxP Tet-off hepatocyte-specific doxycycline 4-OHT C/EBβ

Transcription of the putative tumor suppressor gene HCCS1 requires binding of ETS-2 to its consensus near the transcription start site

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Cell Research 2006年第9期16卷 780-796页

作者： Jing De Zhu~(1,2) Qi Fei~(1,*) Peng Wang~(1,*) Fei Lan~(1,*) Da Qin Mao~(1,*) Hong Yu Zhang~1 Xue Biao Yao~3 1 laboratory of cancer Eplgenetics and gene therapy,The State-Key laboratory for Oncogenes and Related genes,Shanghai cancer Institute,Shanghai Jiaotong University,LN 2200/25,Xietu Road,Shanghai 200032,China 2 School of Life Sciences,Zhejiang Science and Technology University,Xiasha University District,Hangzhou,Zhejiang 310018,China, 3 laboratory of Cellular Dynamics,University of Science and Technology of China,Hefei 230027,China laboratory of cancer epigenetics and gene therapy The State-Key Laboratory for Oncogenes and Related Genes Shanghai Cancer Institute Shanghai Jiaotong University Shanghai China School of Life Sciences Zhejiang Science and Technology University Xiasha University District Hangzhou China laboratory of Cellular Dynamics University of Science and Technology of China Hefei China

The hepatocellular carcinoma suppressor 1 (HCCS1) gene was identified by both positional cloning from a predominantregion of loss of heterozygosity (17p13.3) in liver cancer and by functional screening for genes affecting cell proliferationin large-scale transfection *** overexpression results in inhibition of cell proliferation in cell culture and tumorgrowth in nude *** understand its transcription regulation,the promoter architecture has been dissected in *** start of transcription was mapped by primer extension to a C residue,177 nucleotides upstream of the ATG *** assessing the promoter activity of a set of linker-scanning mutants of the minimal promoter (-60 to +148 region) ina transient transfection assay,we found that the+1 to+40 region is critical to HCCSI gene transcription,containingbinding sites for transcription factors NF-κB(-21 to+7 and+40 to+26),p53 (+29 to+9) and ETS (+4 to+20 and+23to+39).Biochemical and molecular analyses revealed that the ETS transcription factors ETS-2 and Elf-1 bind to thetwo ETS sites in situ and contribute significantly to the transcriptionally active state of the HCCS1 gene,while NF-κB,p53 and two other members of the ETS family (ETS-1 and NERF2) appear to play little *** observations provideinsight into the mechanistic aspects of HCCS1 transcription regulation.

关键词： HCCS1 gene transcription regulation ETS p53 NF-κB

epigenetics(-omics) Takes Center Stage

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Journal of genetics and Genomics 2013年第7期40卷 323-324页

作者： Jingde Zhu cancer epigenetics laboratory Anhui Cancer Hospital107Huanhudonglu cancer epigenetics laboratory Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong UniversityLN 2200/25Xietu Road

epigenetics concerns non-DNA sequence dependent mechanisms through which cross-mitosis （and meiosis） transmission of committed gene expression pattern in high eukaryotes is achieved. The fact that cells with identical genome can have plentiful phenotypic choices suggests a decisive role of epigenetic regulation in selective gene expression and therefore the biological activities at a cell type-specific manner in multi-cellular organisms. In addition to covalent chemical modifications of DNA and the core histones,

关键词： SLC epigenetics Takes Center Stage omics

epigenetics in the modern era of crop improvements

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Science China Life Sciences 2025年

作者： Yan Xue Xiaofeng Cao Xiangsong Chen Xian Deng Xingwang Deng Yong Ding Aiwu Dong Chengguo Duan Xiaofeng Fang Lei Gong Zhizhong Gong Xiaofeng Gu Chongsheng He Hang He Shengbo He Xinjian He Yan He Yuehui He Guifang Jia Danhua Jiang Jianjun Jiang Jinsheng Lai Zhaobo Lang Chenlong Li Qing Li Xingwang Li Bao Liu Bing Liu Xiao Luo Yijun Qi Weiqiang Qian Guodong Ren Qingxin Song Xianwei Song Zhixi Tian Jiawei Wang Yuan Wang Liang Wu Zhe Wu Rui Xia Jun Xiao Lin Xu Zhengyi Xu Wenhao Yan Hongchun Yang Jixian Zhai Yijing Zhang Yusheng Zhao Xuehua Zhong Daoxiu Zhou Ming Zhou Yue Zhou Bo Zhu Jiankang Zhu Qikun Liu College of Life Sciences Institute of Life Science and Green Development Hebei University Biotechnology Research Institute Chinese Academy of Agricultural Sciences College of Biology Hunan Key Laboratory of Plant Functional Genomics and Developmental Regulation Hunan Engineering and Technology Research Center of Hybrid Rapeseed Hunan University Institute of Advanced Agricultural Sciences School of Advanced Agricultural Sciences Peking University State Key laboratory for Conservation and Utilization of Subtropical Agro-Bioresources Guangdong Laboratory for Lingnan Modern Agriculture South China Agricultural University National Institute of Biological Sciences Key laboratory of Seed Innovation Institute of Genetics and Developmental Biology Chinese Academy of Sciences School of Advanced Agricultural Sciences Peking-Tsinghua Center for Life Sciences Peking University Synthetic and Functional Biomolecules Center Beijing National Laboratory for Molecular Sciences Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education College of Chemistry and Molecular Engineering Peking University Key laboratory of Seed Innovation State Key Laboratory of Plant Genomics and National Center for Plant Gene Research Institute of Genetics and Developmental Biology Chinese Academy of Sciences State Key laboratory of Wheat Improvement Peking University Institute of Advanced Agricultural Sciences Shandong Laboratory of Advanced Agricultural Sciences in Weifang State Key laboratory of Crop Stress Adaptation and Improvement School of Life Sciences Henan University State Key laboratory of Maize Bio-breeding National Maize Improvement Center Department of Plant Genetics and Breeding China Agricultural University Frontiers Science Center for Molecular Design Breeding China Agricultural University Center for Crop Functional Genomics and Molecular Breeding China Agricultural University Sanya Institute of China Agricultural University Hainan Yazhou Bay Seed laboratory Institute of Advan

Epigenetic mechanisms are integral to plant growth, development, and adaptation to environmental stimuli. Over the past two decades,our comprehension of these complex regulatory processes has expanded remarkably, producing a substantial body of knowledge on both locus-specific mechanisms and genome-wide regulatory patterns. Studies initially grounded in the model plant Arabidopsis have been broadened to encompass a diverse array of crop species, revealing the multifaceted roles of epigenetics in physiological and agronomic traits. With recent technological advancements, epigenetic regulations at the single-cell level and at the large-scale population level are emerging as new focuses. This review offers an in-depth synthesis of the diverse epigenetic regulations, detailing the catalytic machinery and regulatory functions. It delves into the intricate interplay among various epigenetic elements and their collective influence on the modulation of crop traits. Furthermore, it examines recent breakthroughs in technologies for epigenetic modifications and their integration into strategies for crop improvement. The review underscores the transformative potential of epigenetic strategies in bolstering crop performance, advocating for the development of efficient tools to fully exploit the agricultural benefits of epigenetic insights.

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SUMOylation stabilizes hSSB1 and enhances the recruitment of NBS1 to DNA damage sites

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Signal Transduction and Targeted therapy 2020年第1期5卷 1516-1527页

作者： Liwen Zhou Lisi Zheng Kaishun Hu Xin Wang Ruhua Zhang Yezi Zou Li Zhong Shang Wang Yuanzhong Wu Tiebang Kang Sun Yat-sen University cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060China Guangdong Provincial Key laboratory of Malignant Tumor epigenetics and gene Regulation Medical Research CenterSun Yat-sen Memorial HospitalSun Yat‐sen UniversityGuangzhouChina

Human single-stranded DNA-binding protein 1(hSSB1)is required for the efficient recruitment of the MRN complex to DNA doublestrand breaks and is essential for the maintenance of genome ***,the mechanism by which hSSB1 recruits NBS1 remains ***,we determined that hSSB1 undergoes SUMOylation at both K79 and K94 under normal conditions and that this modification is dramatically enhanced in response to DNA *** of hSSB1,which is specifically fine-tuned by PIAS2α,and SENP2,not only stabilizes the protein but also enhances the recruitment of NBS1 to DNA damage *** with defective hSSB1 SUMOylation are sensitive to ionizing radiation,and global inhibition of SUMOylation by either knocking out UBC9 or adding SUMOylation inhibitors significantly enhances the sensitivity of cancer cells to *** findings reveal that SUMOylation,as a novel posttranslational modification of hSSB1,is critical for the functions of this protein,indicating that the use of SUMOylation inhibitors(e.g.,2-D08 and ML-792)may be a new strategy that would benefit cancer patients being treated with chemo-or radiotherapy.

关键词： SSB1 damage NBS1

Aberrant promoter CpG methylation and its translational applications in breast cancer

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Chinese Journal of cancer 2013年第1期32卷 12-20页

作者： Ting-Xiu Xiang Ying Yuan Li-Li Li Zhao-Hui Wang Liang-Ying Dan Yan Chen Guo-Sheng Ren Qian Tao Molecular Oncology and epigenetics laboratory The First Affiliated Hospital of Chongqing Medical University Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences(CAS)-CUHK cancer epigenetics laboratory Department of Clinical OncologySir YK Pao Center for Cancer and Li Ka Shing Institute of Health SciencesThe Chinese University of Hong Kong Hong Kong and CUHK Shenzhen Research Institute

Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic *** studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant promoter methylation and histone modification,plays a critical role in human breast *** of tumor suppressor genes(TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression,thus directly contributing to breast ***,aberrant promoter methylation of TSGs,which can be reversed by pharmacological reagents,occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast *** this review,we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer.

关键词：临床应用乳腺癌甲基化 CpG 异常子区肿瘤抑制基因肿瘤标志物

Stuxnet detected, Pc breaks down

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Science China(Life Sciences) 2016年第11期59卷 1202-1203页

作者： Xudong Wu Department of Cell Biology 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics Tianjin Key Laboratory of Medical Epigenetics Tianjin Medical University

Polycomb group （PcG） proteins were originally identified in Drosophila. They generally maintain gene silencing by forming multimeric complexes. Two main complexes, namely Polycomb repressive complex 2 （PRC2） and PRC1, have been described. PRC2 methylates histone H3 on lysine 27 （H3K27）. PRC1, mainly composed of Polycomb （Pc）, Polyhomeotic （Ph）, Posterior sex combs （Psc） and dRing/Sce, has been shown to directly compact chromatin in vitro.

关键词： PRC Stuxnet detected UBL Pc breaks down

Zinc-finger protein 382 antagonises CDC25A and ZEB1 signaling pathway in breast cancer

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genes & Diseases 2023年第2期10卷 568-582页

作者： Shuman Li Xiaoqian He Yan Wang Weihong Chen Ran Sun Shaorong Tian Sanxiu He Chunyun Pu Chen Li Dishu Zhou Yu Jiang Qian Tao Lili Li Lin Ye Yue Wu Weiyan Peng Tingxiu Xiang Department of Oncology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Chongqing Key laboratory of Translational Research for cancer Metastasis and Individualized Treatment Chongqing University Cancer HospitalChongqing 400030China Key laboratory of Molecular Oncology and epigenetics The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China cancer epigenetics laboratory Department of Clinical OncologyState Key Laboratory of Translational OncologySir YK Pao Center for CancerLi Ka Shing Institute of Health SciencesThe Chinese University of Hong Kong and CUHK Shenzhen Research InstituteShenzhenGuangdong 518172China

Our previous studies found that Zinc-finger protein 382(ZNF382)played as a tumor suppressor gene in esophageal and gastric cancers,and a positive correlation between the high expression of ZNF382 and better outcome in breast cancer ***,the biological roles and mechanisms of ZNF382 in breast cancer remains *** detected ZNF382 expression by reverse-transcription PCR(RT-PCR)and real-time quantitative PCR(qRT-PCR)in breast cancer cells and tissues,and explored the impacts and mechanisms of ectopic ZNF382 expression in breast cancer cells in vitro and in vivo,*** results revealed that ZNF382 was significantly down-regulated in breast cancer tissues compared with adjacent non-cancer *** of ZNF382 expression in silenced breast cancer cells not only inhibited tumor cell colony formation,viability,migration and invasion,and epithelial-mesenchymal-transition(EMT),but also induced apoptosis and G0/G1 *** conclusion,ZNF382 could induce G0/G1 cell cycle arrest through inhibiting CDC25A signaling,and,inhibit cell migration,invasion and EMT by antagonizing ZEB1 signaling in breast cancer cells.

关键词： Breast cancer CDC25A EMT ZEB1 ZNF382

The emerging role of long noncoding RNA RMRP in cancer development and targeted therapy

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cancer Biology & Medicine 2022年第2期19卷 140-146页

作者： Qian Hao Xiang Zhou Fudan University Shanghai cancer Center and Institutes of Biomedical Sciences Fudan UniversityShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Key laboratory of Breast cancer in Shanghai Fudan University Shanghai Cancer CenterFudan UniversityShanghai 200032China Shanghai Key laboratory of Medical epigenetics International Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)Institutes of Biomedical SciencesFudan UniversityShanghai 200032China

The RNA component of mitochondrial RNA-processing endoribonuclease(RMRP)was first described as an entity that cleaved mitochondrial RNA at a priming site of mitochondrial DNA *** long noncoding RNA(lncRNA)was encoded by an evolutionarily conserved nuclear gene that has been characterized in many species,including human,mouse,cattle,zebrafish,toad,and *** was soon learned that RMRP as a component of the RNase MRP complex was also located in the nucleus,and was critical for ribosomal RNA(rRNA)processing,particularly the biosynthesis of 5.8S *** 2001,the first evidence of the role of RMRP in the pathogenesis of human disorders was reported,involving mutations in the RMRP gene,which caused cartilage-hair hypoplasia(CHH)1,a recessively inherited developmental disorder characterized by short stature,hypoplastic anemia,defective immunity,and predisposition to several cancers.

关键词： immunity anemia pathogenesis

Enhanced CD19 activity in B cells contributes to immunodeficiency in mice deficient in the ICF syndrome gene Zbtb24

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Cellular & Molecular Immunology 2023年第12期20卷 1487-1498页

作者： Zhengzhou Ying Swanand Hardikar Joshua B.Plummer Tewfik Hamidi Bin Liu Yueping Chen Jianjun Shen Yunxiang Mu Kevin M.McBride Taiping Chen Department of epigenetics and Molecular Carcinogenesis The University of Texas MD Anderson Cancer CenterHoustonTX77030USA Program in genetics and epigenetics The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical SciencesHoustonTX77030USA

Immunodeficiency,centromeric instability,and facial anomalies(ICF)syndrome is a rare autosomal recessive disorder characterized by DNA hypomethylation and antibody *** is caused by mutations in DNMT3B,ZBTB24,CDCA7,or *** progress has been made in elucidating the roles of these genes in regulating DNA methylation,little is known about the pathogenesis of the life-threatening hypogammaglobulinemia ***,we show that mice deficient in Zbtb24 in the hematopoietic lineage recapitulate the major clinical features of patients with ICF ***,Vav-Cre-mediated ablation of Zbtb24 does not affect lymphocyte development but results in reduced plasma cells and low levels of IgM,IgG1,and ***24-deficient mice are hyper and hypo-responsive to T-dependent and T-independent type 2 antigens,respectively,and marginal zone B-cell activation is ***,Zbtb24-deficient B cells show severe loss of DNA methylation in the promoter region of Il5ra(interleukin-5 receptor subunit alpha),and Il5ra derepression leads to elevated CD19 *** disruption of Cd19 can revert the hypogammaglobulinemia phenotype of Zbtb24-deficient *** results suggest the potential role of enhanced CD19 activity in immunodeficiency in ICF syndrome.

关键词： ICF syndrome ZBTB24 CD19 IL-5Ra hypogammaglobulinemia