Dataset Information

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

ABSTRACT:

Background

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.

Results

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.

Conclusions

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.

SUBMITTER: Zhao C

PROVIDER: S-EPMC7667739 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Zhao Chengchen C Zhang Naiqian N Zhang Yalin Y Tuersunjiang Nuermaimaiti N Gao Shaorong S Liu Wenqiang W Zhang Yong Y

Genome biology 20201116 1

<h4>Background</h4>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.<h4>Results</h4>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 ...[more]

PMID: 33198783

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Project description:BackgroundIntergenic transcription, either failure to terminate at the transcription end site (TES), or transcription initiation at other intergenic regions, is present in cultured cells and enhanced in the presence of stressors such as viral infection. Transcription termination failure has not been characterized in natural biological samples such as pre-implantation embryos which express more than 10,000 genes and undergo drastic changes in DNA methylation.ResultsUsing Automatic Readthrough Transcription Detection (ARTDeco) and data of in vivo developed bovine oocytes and embryos, we found abundant intergenic transcripts that we termed as read-outs (transcribed from 5 to 15 kb after TES) and read-ins (transcribed 1 kb up-stream of reference genes, extending up to 15 kb up-stream). Read-throughs (continued transcription from TES of expressed reference genes, 4-15 kb in length), however, were much fewer. For example, the numbers of read-outs and read-ins ranged from 3,084 to 6,565 or 33.36-66.67% of expressed reference genes at different stages of embryo development. The less copious read-throughs were at an average of 10% and significantly correlated with reference gene expression (P < 0.05). Interestingly, intergenic transcription did not seem to be random because many intergenic transcripts (1,504 read-outs, 1,045 read-ins, and 1,021 read-throughs) were associated with common reference genes across all stages of pre-implantation development. Their expression also seemed to be regulated by developmental stages because many were differentially expressed (log2 fold change ≥ 2, P < 0.05). Additionally, while gradual but un-patterned decreases in DNA methylation densities 10 kb both up- and down-stream of the intergenic transcribed regions were observed, the correlation between intergenic transcription and DNA methylation was insignificant. Finally, transcription factor binding motifs and polyadenylation signals were found in 27.2% and 12.15% of intergenic transcripts, respectively, suggesting considerable novel transcription initiation and RNA processing.ConclusionIn summary, in vivo developed oocytes and pre-implantation embryos express large numbers of intergenic transcripts, which are not related to the overall DNA methylation profiles either up- or down-stream.

Dataset Information

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

Background

Results

Conclusions

Publications

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

Similar Datasets

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