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Landscape and Dynamics of the Transcriptional Regulatory Network During Natural Killer Cell Differentiation

查看全文 作　　者：Kun [1]Li;Yang [1]Wu;Young [1]Li;Qiaoni [1]Yu;Zhigang [1,2]Tian;Haiming [1,2]Wei;Kun [1,2,3]Qu 高影响力作者 机构地区：[1]Department of Oncology,The First Affiliated Hospital of USTC,Division of Molecular Medicine,Hefei National Laboratory for Physical Sciences at Microscale,School of Basic Medical Sciences,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230021,China;[2]CAS Center for Excellence in Molecular Cell Sciences,The CAS Key Laboratory of Innate Immunity and Chronic Disease,University of Science and Technology of China,Hefei 230027,China;[3]School of Data Science,University of Science and Technology of China,Hefei 230026,China高影响力机构 出　　处：《Genomics, Proteomics & Bioinformatics》索引2020年第18卷第5期,共15页高影响力期刊 基　　金：supported by the National Key R&D Program of China(Grant No.2017YFA0102900)to KQ;the National Natural Science Foundation of China(Grant Nos.91640113,91940306,31771428,and 31970858 to KQ,as well as 81330071 to HW);supported by the Fundamental Research Funds for the Central Universities,China(Grant Nos.YD2070002019,WK2070000158,and WK9110000141)to KQ。 摘　　要：Natural killer(NK)cells are essential in controlling cancer and infection.However,little is known about the dynamics of the transcriptional regulatory machinery during NK cell differentiation.In this study,we applied the assay of transposase accessible chromatin with sequencing(ATAC-seq)technique in a home-developed in vitro NK cell differentiation system.Analysis of ATAC-seq data illustrated two distinct transcription factor(TF)clusters that dynamically regulate NK cell differentiation.Moreover,two TFs from the second cluster,FOS-like 2(FOSL2)and early growth response 2(EGR2),were identified as novel essential TFs that control NK cell maturation and function.Knocking down either of these two TFs significantly impacted NK cell differentiation.Finally,we constructed a genome-wide transcriptional regulatory network that provides a better understanding of the regulatory dynamics during NK cell differentiation. 关 键 词：NK cell ATAC-seq Programmed differentiation FOSL2 EGR2 Dynamic regulatory network
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