Visualization of aging-associated chromatin alterations with an engineered TALE system

查看全文 作　　者：Ruotong [1,2]Ren;Liping [1,2,3]Deng;Yanhong [1,2]Xue;Keiichiro [4]Suzuki;Weiqi [1,2]Zhang;Yang [5]Yu;Jun [4]Wu;Liang [6]Sun;Xiaojun [7]Gong;Huiqin [1]Luan;Fan [8]Yang;Zhenyu [9]Ju;Xiaoqing [1]Ren;Si [1]Wang;Hong [7]Tang;Lingling [1]Geng;Weizhou [10]Zhang;Jian [6]Li;Jie [5]Qiao;Tao [1,2]Xu;Jing [2,3]Qu;Guang-Hui [1,2,8,11]Liu

机构地区：[1]National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;[2]University of Chinese Academy of Sciences, Beijing 100049, China;[3]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;[4]Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA;[5]Department of Gynecology and Obstetrics', Peking University Third Hospital, Beijing 100191, China;[6]The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, China;[7]Department of Pediatrics, Beijing Shijitan Hospital Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing 100038, China;[8]Key Laborato- ry of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, Guangdong 510632, China;[9]Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang 311121, China;[10]Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA;[11]HBeijing Institute for Brain Disorders, Beij'ing 100069, China

出　　处：《Cell Research》索引2017年第27卷第4期,共22页

基　　金：We thank Drs Lusheng Gu and Wei Ji and the Center for Bio- logical Instrument Development (CBID), Institute of Biophysics, Chinese Academy of Sciences (CAS), for their help in analyzing CLEM images, as well as Shuoguo Li and Center for Biological Imaging (CBI), Institute of Biophysics, CAS, for technical as- sistance in SIM imaging. We are grateful to Yang Zhao and Lei Bai for administrative assistance. This work was supported by the National Basic Research Program of China (973 Program; 2015CB964800, 2014CB910503 and 2014CB964600), the Nation- al High Technology Research and Development Program of China (2015AA020307), CAS (XDA01020312, KJZDEW-TZ-L05, and CXJJ-16M271), the National Natural Science Foundation of China (NSFC; 81625009, 81330008, 31222039, 81371342, 81300261, 81300677, 81271266, 81471414, 81422017, 81401159, 31671429, 81601233, 81671377, 31601109, and 31601158), Beijing Natural Science Foundation (7141005 and 5142016), Pro- gram of Beijing Municipal Science and Technology Commission (Z 151100003915072), Key Research Program of the Chinese Academy of Sciences (KJZDEW-TZ-L05), the Thousand Young Talents Program of China, and the State Key Laboratory of Stem Cell and Reproductive Biology (2016SRLabKF13). TX was sup- ported by NSFC (31127901, 31421002, 81427802, and 31130065) and the Instrument Developing Project of the Chinese Acade- my of Sciences (YZ201443). ZYJ was supported by the NSFC (81420108017 and 81525010) and the National Basic Research Program of China (973 Program; 2016YFA0100600). WZ was supported by Youth Innovation Promotion Association of CAS and Early Career Fellowship of Chinese Society of Cell Biology. JQ was supported by the NSFC (31230047) and the National Ba- sic Research Program of China (973 Program; 2014CB943203). LS was supported by NSFC (81571385). YY was supported by the Key Special Fund (2016YFC1000601), the National Basic Research Program of China (973 Program; 2014CB943203) and Beijing Nova Program (xxjh2015011). WZ was supported by NIH grants CA158055, CA200673, and CA203834, the V Scholar award, American Cancer Society seed grant, Breast Cancer Research Award and Oberley Award (National Cancer Institute Award P30CA086862) from Holden Comprehensive Cancer Center at the University of Iowa. 摘　　要：在实时房间的特定的 genomic loci 的可视化在多样的生物过程期间是为在染色质建筑学的动态变化的调查的一个前提,例如细胞的老化。然而,当前的精确 genomic 成像方法被缺乏妨碍荧光灯有高特性和 signal-to-noise 的探针形成对照。我们发现那常规抄写像使活跃之物的受动器(故事) 趋于形成蛋白质总数,从而在成像应用程序损害他们的性能。通过屏蔽,我们发现有故事的那熔化 thioredoxin 阻止了总数形成,开基于故事的 genomic 成像的完整的力量。用熔化 thioredoxin 的故事(TTALE ) ,我们在各种各样的 genomic loci 完成了高质量的成像并且观察联系老化(epi ) 在在人和老鼠早衰模型的 telomeres 和着丝点的 genomic 改变。重要地,我们鉴别 ribosomal DNA 的摩擦为人的老化作为一个分子的标记重复。我们的学习为精确在 vitro 并且在 vivo 监视染色质动力学建立一个简单、柔韧的成像方法。 关键词：可视化染色质故事 DNA重复序列成像方法硫氧还蛋白系统工程

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Visualization of aging-associated chromatin alterations with an engineered TALE system

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