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bioRxiv · 10.1101/470963

Simultaneous profiling of DNA methylation and chromatin architecture in mixed populations and in single cells

Ren, B.·Li, G.·Liu, Y.·Fang, R.·Kellis, M.·Zhang, Y.
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Abstract

Dynamic DNA methylation and three-dimensional chromatin architecture compose a major portion of a cells epigenome and play an essential role in tissue specific gene expression programs. Currently, DNA methylation and chromatin organization are generally profiled in separate assays. Here, we report Methyl-HiC, a method combining in situ Hi-C and whole genome bisulfite sequencing (WGBS) to simultaneously capture chromosome conformation and DNA methylome in a single assay. Methyl-HiC analysis of mouse embryonic stem cells reveals coordinated DNA methylation between distant yet spatially proximal genomic regions. Extension of Methyl-HiC to single cells further enables delineation of the heterogeneity of both chromosomal conformation and DNA methylation in a mixed cell population, and uncovers increased dynamics of chromatin contacts and decreased stochasticity in DNA methylation in genomic regions that replicate early during cell cycle.

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Ren, B., Li, G., Liu, Y., Fang, R., Kellis, M., Zhang, Y.. 2018-11-14. Simultaneous profiling of DNA methylation and chromatin architecture in mixed populations and in single cells. https://doi.org/10.1101/470963

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