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

作     者：Kun Li Yang Wu Young Li Qiaoni Yu Zhigang Tian Haiming Wei Kun Qu Kun Li;Yang Wu;Young Li;Qiaoni Yu;Zhigang Tian;Haiming Wei;Kun Qu

作者机构：Department of OncologyThe First Affiliated Hospital of USTCDivision of Molecular MedicineHefei National Laboratory for Physical Sciences at MicroscaleSchool of Basic Medical SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230021China CAS Center for Excellence in Molecular Cell SciencesThe CAS Key Laboratory of Innate Immunity and Chronic DiseaseUniversity of Science and Technology of ChinaHefei 230027China School of Data ScienceUniversity of Science and Technology of ChinaHefei 230026China 

出 版 物：《Genomics, Proteomics & Bioinformatics》 (基因组蛋白质组与生物信息学报（英文版）)

年 卷 期：2020年第18卷第5期

页      面：501-515页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 0714[理学-统计学（可授理学、经济学学位）] 0703[理学-化学] 0701[理学-数学] 10[医学] 0812[工学-计算机科学与技术（可授工学、理学学位）] 

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。 

主　　题：NK cell ATAC-seq Programmed differentiation FOSL2 EGR2 Dynamic regulatory network 

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.