Precision Methylome and In Vivo Methylation Kinetics Characterization of Klebsiella pneumoniae  

作　　者：Jing Fu Ju Zhang Li Yang Nan Ding Liya Yue Xiangli Zhang Dandan Lu Xinmiao Jia Cuidan Li Chongye Guo Zhe Yin Xiaoyuan Jiang Yongliang Zhao Fei Chen Dongsheng Zhou 

机构地区：[1]CAS Key Laboratory of Genome Sciences and Information,Beijing Institute of Genomics,Chinese Academy of Sciences and China National Center for Bioinformation,Beijing 100101,China [2]Department of Oncology,Henan Provincial People’s Hospital,People’s Hospital of Zhengzhou University,People’s Hospital of Henan University,Zhengzhou 450001,China [3]University of Chinese Academy of Sciences,Beijing 100049,China [4]Department of Medical Research Center,Peking Union Medical College Hospital,Peking Union Medical College&Chinese Academy of Medical Sciences,Beijing 100730,China [5]State Key Laboratory of Pathogen and Biosecurity,Beijing Institute of Microbiology and Epidemiology,Beijing 100071,China [6]CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences and China National Center for Bioinformation,Beijing 100101,China

出　　处：《Genomics, Proteomics & Bioinformatics》2022年第2期418-434,共17页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by the National Key Program for Infectious Disease of China(Grant No.2018ZX10302301-004-003);the National Natural Science Foundation of China(Grant Nos.31770870 and 31801093).

摘　　要：Klebsiella pneumoniae(K.pneumoniae)is an important pathogen that can cause severe hospital-and community-acquired infections.To systematically investigate its methylation features,we determined the whole-genome sequences of 14 K.pneumoniae strains covering varying serotypes,multilocus sequence types,clonal groups,viscosity/virulence,and drug resistance.Their methylomes were further characterized using Pacific Biosciences single-molecule real-time and bisulfite technologies.We identified 15 methylation motifs[13 N6-methyladenine(6mA)and two 5-methylcytosine(5mC)motifs],among which eight were novel.Their corresponding DNA methyltransferases were also validated.Additionally,we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains,and identified differential distribution patterns of some hemi-/un-methylated GATC motifs,which tend to be located within intergenic regions(IGRs).Specifically,we characterized the in vivo methylation kinetics at single-base resolution on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation.The slow methylation of the GATC motifs in the replication origin(oriC)regions and IGRs implicates the epigenetic regulation of replication initiation and transcription.Our findings illustrate the first comprehensive dynamic methylome map of K.pneumoniae at single-base resolution,and provide a useful reference to better understand epigenetic regulation in this and other bacterial species.

关 键 词：DNA methylation EPIGENOMICS 6mA 5mC Epigenetic regulation 

分 类 号：R378[医药卫生—病原生物学]