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A DNA methylation state transition model reveals the programmed epigenetic heterogeneity in human pre-implantation embryos

Zhao, Chengchen ; Zhang, Naiqian ; Zhang, Yalin ; Tuersunjiang, Nuermaimaiti ; Gao, Shaorong ; Liu, Wenqiang ; Zhang, Yong

Genome Biology, 2020-11, Vol.21 (1), p.277-277, Article 277 [Peer Reviewed Journal]

England: BioMed Central

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Title:
A DNA methylation state transition model reveals the programmed epigenetic heterogeneity in human pre-implantation embryos
Author: Zhao, Chengchen ; Zhang, Naiqian ; Zhang, Yalin ; Tuersunjiang, Nuermaimaiti ; Gao, Shaorong ; Liu, Wenqiang ; Zhang, Yong
Subjects: Animals ; Cell cycle ; Cell fate ; Chromosomal Proteins, Non-Histone ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Embryo, Mammalian ; Embryogenesis ; Embryonic Development - genetics ; Embryos ; Enzymes ; Epigenesis, Genetic ; Epigenetics ; Epigenome ; Epigenomics ; First cell fate determination ; Gene expression ; Genetic Heterogeneity ; Heterogeneity ; Humans ; Mathematical models ; Mice ; Models, Biological ; Parameter estimation ; Partial differential equations ; Probability ; Promoter Regions, Genetic
Is Part Of: Genome Biology, 2020-11, Vol.21 (1), p.277-277, Article 277
Notes: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Description: During mammalian early embryogenesis, expression and epigenetic heterogeneity emerge before the first cell fate determination, but the programs causing such determinate heterogeneity are largely unexplored. Here, we present MethylTransition, a novel DNA methylation state transition model, for characterizing methylation changes during one or a few cell cycles at single-cell resolution. MethylTransition involves the creation of a transition matrix comprising three parameters that represent the probabilities of DNA methylation-modifying activities in order to link the methylation states before and after a cell cycle. We apply MethylTransition to single-cell DNA methylome data from human pre-implantation embryogenesis and elucidate that the DNA methylation heterogeneity that emerges at promoters during this process is largely an intrinsic output of a program with unique probabilities of DNA methylation-modifying activities. Moreover, we experimentally validate the effect of the initial DNA methylation on expression heterogeneity in pre-implantation mouse embryos. Our study reveals the programmed DNA methylation heterogeneity during human pre-implantation embryogenesis through a novel mathematical model and provides valuable clues for identifying the driving factors of the first cell fate determination during this process.
Publisher: England: BioMed Central
Language: English

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A DNA methylation state transition model reveals the programmed epigenetic heterogeneity in human pre-implantation embryos

Zhao, Chengchen ; Zhang, Naiqian ; Zhang, Yalin ; Tuersunjiang, Nuermaimaiti ; Gao, Shaorong ; Liu, Wenqiang ; Zhang, Yong

England: BioMed Central

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