期刊
NUCLEIC ACIDS RESEARCH
卷 42, 期 22, 页码 13488-13499出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gku1097
关键词
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资金
- National Basic Research Program of China [2012CB316504, 2012CB518702]
- National Natural Science Foundation of China [91010016]
- Tsinghua University Collaborative Research Program [2011Z23153]
- Center for Marine Medicine and Rescue of Tsinghua University [20124812029]
- Bill and Melinda Gates Foundation [OPP1021992]
- Bill and Melinda Gates Foundation [OPP1021992] Funding Source: Bill and Melinda Gates Foundation
In an isogenic cell population, phenotypic heterogeneity among individual cells is common and critical for survival of the population under different environment conditions. DNA modification is an important epigenetic factor that can regulate phenotypic heterogeneity. The single molecule real-time (SMRT) sequencing technology provides a unique platform for detecting a wide range of DNA modifications, including N6-methyladenine (6-mA), N4-methylcytosine (4-mC) and 5-methylcytosine (5-mC). Here we present qDNAmod, a novel bioinformatic tool for genome-wide quantitative profiling of intercellular heterogeneity of DNA modification from SMRT sequencing data. It is capable of estimating proportion of isogenic haploid cells, in which the same loci of the genome are differentially modified. We tested the reliability of qDNAmod with the SMRT sequencing data of Streptococcus pneumoniae strain ST556. qDNAmod detected extensive intercellular heterogeneity of DNA methylation (6-mA) in a clonal population of ST556. Subsequent biochemical analyses revealed that the recognition sequences of two type I restriction-modification (R-M) systems are responsible for the intercellular heterogeneity of DNA methylation initially identified by qDNAmod. qDNAmod thus represents a valuable tool for studying intercellular phenotypic heterogeneity from genome-wide DNA modification.
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