Cellular type is a major determinant of R-loop genomic distribution

Abstract

R-loops containing a DNA:RNA hybrid and unpaired single-stranded DNA are important for normal cell physiology and pathogenesis of numerous diseases. Although several different approaches for R-loop mapping have been developed, these techniques can produce conflicting results. In order to assess their robustness, a study by Chedin et al compared a number of R-loop datasets obtained using different methodologies from normal and cancer cell lines. That study assumed a high degree of similarity between R-loop genomic distributions across different cell types. Here, comparing DRIP datasets produced using the same protocol in different cell lines; we show that only 26 percent of R-loop peaks are common between a chronic myeloid leukemiaderived HAP1 and human pluripotent stem cells, whereas HAP1-derived knockout cell lines share substantial fractions of R-loop peaks with their parental line. We conclude that cellular type represents a major determinant of R-loop genomic distribution and, therefore, only a systematic comparison of a large array of various cell/tissue-types-derived R-loop datasets may address the inconsistencies between different R-loop mapping techniques.