Decision letter: High-resolution, genome-wide mapping of positive supercoiling in chromosomes [peer_review]

James M Berger, Naama Barkai
2021 unpublished
Supercoiling impacts DNA replication, transcription, protein binding to DNA, and the three-dimensional organization of chromosomes. However, there are currently no methods to directly interrogate or map positive supercoils, so their distribution in genomes remains unknown. Here, we describe a method, GapR-seq, based on the chromatin immunoprecipitation of GapR, a bacterial protein that preferentially recognizes overtwisted DNA, for generating high-resolution maps of positive supercoiling.
more » ... ng this method to Escherichia coli and Saccharomyces cerevisiae, we find that positive supercoiling is widespread, associated with transcription, and particularly enriched between convergently oriented genes, consistent with the 'twin-domain' model of supercoiling. In yeast, we also find positive supercoils associated with centromeres, cohesin-binding sites, autonomously replicating sites, and the borders of R-loops (DNA-RNA hybrids). Our results suggest that GapR-seq is a powerful approach, likely applicable in any organism, to investigate aspects of chromosome structure and organization not accessible by Hi-C or other existing methods. Guo et al. eLife 2021;10:e67236. DOI: https://doi.org/10.7554/eLife.67236 1 of 34 RESEARCH ARTICLE Guo et al. eLife 2021;10:e67236.
doi:10.7554/elife.67236.sa1 fatcat:btilblvf4fddxhpaqottsd4br4