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Simultaneous profiling of transcriptome and DNA methylome from a single cell.
Youjin Hu1,2, Kevin Huang1,3, Qin An1
1Department of Human Genetics, David Geffen School of Medicine, UCLA, 695 Charles Young Drive South, Los Angeles, CA, 90095, USA.
Genome Biology
|May 7, 2016
Summary
A new method, scMT-seq, simultaneously measures DNA methylation and gene expression in single cells. This reveals gene body methylation positively correlates with expression for genes with CpG island promoters, clarifying epigenetic regulation mechanisms.
Area of Science:
- Epigenetics
- Genomics
- Molecular Biology
Background:
- Single-cell transcriptome and methylome technologies offer genome-wide insights into RNA and DNA methylation.
- Understanding the direct correlation between DNA methylation and gene expression within single cells remains a challenge due to cell variability and lack of simultaneous measurements.
- The precise association between DNA methylation and gene expression at the single-cell level is still unclear.
Purpose of the Study:
- To develop and present a novel method for simultaneous profiling of DNA methylome and transcriptome from individual cells.
- To investigate the relationship between DNA methylation and gene expression heterogeneity in single sensory neurons.
- To explore the impact of promoter and gene body methylation on gene expression, considering CpG island presence.
Main Methods:
- Development of scMT-seq, a novel method for simultaneous single-cell DNA methylome and transcriptome profiling.
- Application of scMT-seq to sensory neurons to analyze transcriptome and methylome heterogeneity.
- Utilizing single nucleotide polymorphism (SNP) patterns from a hybrid mouse model to assess allelic methylation and expression.
Main Results:
- scMT-seq enables simultaneous transcriptome and methylome profiling from the same single cell.
- In sensory neurons, most expression variance is not linked to proximal promoter methylation, except for genes lacking CpG islands.
- Gene body methylation positively correlates with gene expression for genes with CpG island promoters.
- Allelic gene body methylation shows a positive correlation with allelic expression, as evidenced by SNP analysis.
Conclusions:
- The scMT-seq method allows for the simultaneous detection of transcriptome, methylome, and SNP information within single cells.
- This approach facilitates the dissection of mechanisms underlying epigenetic gene regulation.
- Provides a powerful tool for understanding the interplay between DNA methylation and gene expression at a single-cell resolution.
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