Gaining insights into the regulatory mechanisms that underlie the 
transcriptional variation observed between individual cells necessitates the 
development of methods that measure chromatin organization in single cells. Here 
I adapted Nucleosome Occupancy and Methylome-sequencing (NOMe-seq) 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). An advantage of 
scNOMe-seq is that sequencing reads are sampled independently of the 
accessibility measurement. scNOMe-seq therefore controlled for fragment loss, 
which enabled direct estimation of the fraction of accessible DHSs within 
individual cells. In addition, scNOMe-seq provided high resolution of chromatin 
accessibility within individual loci which was exploited to detect footprints of 
CTCF binding events and to estimate the average nucleosome phasing distances in 
single cells. scNOMe-seq is therefore well-suited to characterize the chromatin 
organization of single cells in heterogeneous cellular mixtures.