PT  - JOURNAL ARTICLE
AU  - Sebastian Pott
TI  - Simultaneous measurement of chromatin accessibility, DNA methylation, and nucleosome phasing in single cells
AID  - 10.1101/061739
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 061739
4099  - http://biorxiv.org/content/early/2016/07/01/061739.short
4100  - http://biorxiv.org/content/early/2016/07/01/061739.full
AB  - Gaining insights into the regulatory mechanisms that underlie the pervasive transcriptional variation observed between individual cells1,2 necessitates the development of methods that measure chromatin organization in single cells. Nucleosome Occupancy and Methylome-sequencing (NOMe-seq) employs a GpC methyltransferase to detect accessible chromatin and has been used to map nucleosome positioning and DNA methylation genome-wide in bulk samples3,4. Here I provide proof-of-principle that NOMe-seq can be adapted to measure chromatin accessibility and endogenous DNA methylation in single cells (scNOMe-seq). scNOMe-seq recovered characteristic accessibility and DNA methylation patterns at DNase hypersensitive sites (DHSs) and enabled direct estimation of the fraction of accessible DHSs within an individual cell. In addition, scNOMe-seq provided high resolution of chromatin accessibility within individual loci which was exploited to detect footprints of CTCF binding and to estimate the average nucleosome phasing distances in single cells. This approach could be applied to characterize the chromatin organization of single cells in heterogeneous mixtures of cells, for example to samples of primary cancer cells.