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BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates.

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收录情况： ◇ SCIE

作者：
Liang Chuqian[1,2,3,4] * ; Ke Qiong[5,6] * ; Liu Zunpeng[7,2,3] * ; Ren Jie[2,8,9,3,10] * ; Zhang Weiqi[2,8,9,3,10] * ; Hu Jianli[8,3] ; Wang Zehua[7,2,3] ; Chen Hong[5] ; Xia Kai[5] ; Lai Xingqiang[11] ; Wang Qiaoran[8,3] ; Yang Kuan[8,3,10] ; Li Wei[12,13] ; Wu Zeming[1,2,3] ; Wang Chao[5,6] ; Yan Haoteng[12,13] ; Jiang Xiaoyu[1,3] ; Ji Zhejun[7,2,14] ; Ma Miyang[1,3] ; Long Xiao[15] ; Wang Si[12,13,16] ; Wang Huating[17] ; Sun Hao[18] ; Belmonte Juan Carlos Izpisua[19] ; Qu Jing[7,2,3,14] ; Xiang Andy Peng[5,20] ; Liu Guang-Hui[1,2,3,4,14,12,13] ;
机构： [1]State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. [2]Institute for Stem cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. [3]University of Chinese Academy of Sciences, Beijing 100049, China. [4]National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. [5]Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China. [6]Department of Genetics and Cell Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China. [7]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. [8]CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China. [9]China National Center for Bioinformation, Beijing 100101, China. [10]Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100049, China. [11]Cardiovascular Department, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518033, China. [12]Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China. [13]Aging Translational Medicine Center, International Center for Aging and Cancer, Xuanwu Hospital, Capital Medical University, Beijing 100053, China. [14]Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China. [15]Division of Plastic Surgery, Peking Union Medical College Hospital, Beijing 100032, China. [16]Chongqing Renji Hospital, University of Chinese Academy of Sciences, Chongqing 400062, China. [17]Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China. [18]Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China. [19]Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. [20]Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
出处：
DOI： 10.1093/nar/gkac146
ISSN：

摘要：
Aging in humans is intricately linked with alterations in circadian rhythms concomitant with physiological decline and stem cell exhaustion. However, whether the circadian machinery directly regulates stem cell aging, especially in primates, remains poorly understood. In this study, we found that deficiency of BMAL1, the only non-redundant circadian clock component, results in an accelerated aging phenotype in both human and cynomolgus monkey mesenchymal progenitor cells (MPCs). Unexpectedly, this phenotype was mainly attributed to a transcription-independent role of BMAL1 in stabilizing heterochromatin and thus preventing activation of the LINE1-cGAS-STING pathway. In senescent primate MPCs, we observed decreased capacity of BMAL1 to bind to LINE1 and synergistic activation of LINE1 expression. Likewise, in the skin and muscle tissues from the BMAL1-deficient cynomolgus monkey, we observed destabilized heterochromatin and aberrant LINE1 transcription. Altogether, these findings uncovered a noncanonical role of BMAL1 in stabilizing heterochromatin to inactivate LINE1 that drives aging in primate cells.© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

基金：
National Key Research and Development Program of China [2020YFA0804000, 2018YFA0107203]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16000000]; National Natural Science Foundation of China [81861168034, 81921006, 81625009, 91949209, 92049304, 81822018, 82071588, 92049116, 82125011, 82122024, 32100937, 92149301, 92168201]; National Key Research and Development Program of China [2018YFC2000100, 2020YFA0112200]; Key Research Program of the Chinese Academy of Sciences [KFZD-SW-221]; Program of the Beijing Natural Science Foundation [Z190019]; K.C. Wong Education Foundation [GJTD-2019-06, GJTD-2019-08]; Key-Area Research and Development Program of Guangdong Province [2019B020235002]; Youth Innovation Promotion Association of CAS [2021078, E1CAZW0401]; Informatization Plan of Chinese Academy of Sciences [WX145XQ07-18; CAS-WX2021SF-0301]; State Key Laboratory of Stem Cell and Reproductive Biology; State Key Laboratory of Membrane Biology; Tencent Foundation [2021-1045]; Milky Way Research Foundation (MWRF). Funding for open access charge: National Key Research and Development Program of China [2020YFA0804000].
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
最新[2025]版：
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
JCR分区：
出版当年[2020]版：
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版：
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. [2]Institute for Stem cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. [3]University of Chinese Academy of Sciences, Beijing 100049, China. [4]National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
共同第一作者：
通讯作者：
通讯机构： [1]State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. [2]Institute for Stem cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. [3]University of Chinese Academy of Sciences, Beijing 100049, China. [4]National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. [5]Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China. [7]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. [12]Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China. [13]Aging Translational Medicine Center, International Center for Aging and Cancer, Xuanwu Hospital, Capital Medical University, Beijing 100053, China. [14]Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China. [20]Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
推荐引用方式(GB/T 7714)：
Liang Chuqian,Ke Qiong,Liu Zunpeng,et al.BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates.[J].NUCLEIC ACIDS RESEARCH.2022,50(6):3323-3347.doi:10.1093/nar/gkac146.
APA：
Liang Chuqian,Ke Qiong,Liu Zunpeng,Ren Jie,Zhang Weiqi...&Liu Guang-Hui.(2022).BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates..NUCLEIC ACIDS RESEARCH,50,(6)
MLA：
Liang Chuqian,et al."BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates.".NUCLEIC ACIDS RESEARCH 50..6(2022):3323-3347

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