PT  - JOURNAL ARTICLE
AU  - Guoqiang Li
AU  - Yaping Liu
AU  - Yanxiao Zhang
AU  - Rongxin Fang
AU  - Manolis Kellis
AU  - Bing Ren
TI  - Simultaneous profiling of DNA methylation and chromatin architecture in mixed populations and in single cells
AID  - 10.1101/470963
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 470963
4099  - http://biorxiv.org/content/early/2018/11/15/470963.short
4100  - http://biorxiv.org/content/early/2018/11/15/470963.full
AB  - Dynamic DNA methylation and three-dimensional chromatin architecture compose a major portion of a cell’s 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.