Using DNA–RNA immunoprecipitation followed by cDNA conversion coupled to high-throughput sequencing (DRIPc–seq), researchers have profiled the genome-wide prevalence and distribution of R loops in mouse and human cells. Mapping of R loops at near base-pair resolution and in a strand-specific manner showed that the co-transcriptional hybridization of nascent RNAs to template DNA is a conserved, prevalent and dynamic feature of mammalian chromatin that can impact gene expression. Epigenomic profiling revealed that R loops associate with specific epigenomic signatures: at promoters, R loops associate with an open, histone H3 lysine 4 (H3K4) hypermethylated and hyperacetylated state characteristic of strong CpG island promoters; at terminators, R loops associate with an enhancer- and insulator-like state; and R-loop formation seems to be a conserved hallmark of a broad class of transcription terminators.