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 ...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.展开更多
基金supported by the National Key R&D Program of China(Grant No.2017YFA0102900)to KQthe 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。
文摘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.
