PMID- 33385611 OWN - NLM STAT- MEDLINE DCOM- 20211025 LR - 20211025 IS - 2210-3244 (Electronic) IS - 1672-0229 (Print) IS - 1672-0229 (Linking) VI - 18 IP - 5 DP - 2020 Oct TI - Landscape and Dynamics of the Transcriptional Regulatory Network During Natural Killer Cell Differentiation. PG - 501-515 LID - S1672-0229(20)30166-2 [pii] LID - 10.1016/j.gpb.2020.12.003 [doi] AB - 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. CI - Copyright (c) 2020 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Li, Kun AU - Li K AD - 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. FAU - Wu, Yang AU - Wu Y AD - 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. FAU - Li, Young AU - Li Y AD - 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. FAU - Yu, Qiaoni AU - Yu Q AD - 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. FAU - Tian, Zhigang AU - Tian Z AD - 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; 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. FAU - Wei, Haiming AU - Wei H AD - 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; 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. Electronic address: ustcwhm@ustc.edu.cn. FAU - Qu, Kun AU - Qu K AD - 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; 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; School of Data Science, University of Science and Technology of China, Hefei 230026, China. Electronic address: qukun@ustc.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201230 PL - England TA - Genomics Proteomics Bioinformatics JT - Genomics, proteomics & bioinformatics JID - 101197608 RN - 0 (Chromatin) SB - IM MH - Cell Differentiation MH - *Chromatin MH - *High-Throughput Nucleotide Sequencing MH - Killer Cells, Natural MH - Sequence Analysis, DNA PMC - PMC8377244 OTO - NOTNLM OT - ATAC-seq OT - Dynamic regulatory network OT - EGR2 OT - FOSL2 OT - NK cell OT - Programmed differentiation EDAT- 2021/01/02 06:00 MHDA- 2021/10/26 06:00 PMCR- 2020/12/30 CRDT- 2021/01/01 20:08 PHST- 2018/08/01 00:00 [received] PHST- 2018/12/10 00:00 [revised] PHST- 2019/03/04 00:00 [accepted] PHST- 2021/01/02 06:00 [pubmed] PHST- 2021/10/26 06:00 [medline] PHST- 2021/01/01 20:08 [entrez] PHST- 2020/12/30 00:00 [pmc-release] AID - S1672-0229(20)30166-2 [pii] AID - 10.1016/j.gpb.2020.12.003 [doi] PST - ppublish SO - Genomics Proteomics Bioinformatics. 2020 Oct;18(5):501-515. doi: 10.1016/j.gpb.2020.12.003. Epub 2020 Dec 30.