Title |
DNA Topoisomerase I differentially modulates R-loops across the human genome
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Published in |
Genome Biology, July 2018
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DOI | 10.1186/s13059-018-1478-1 |
Pubmed ID | |
Authors |
Stefano G. Manzo, Stella R. Hartono, Lionel A. Sanz, Jessica Marinello, Sara De Biasi, Andrea Cossarizza, Giovanni Capranico, Frederic Chedin |
Abstract |
Co-transcriptional R-loops are abundant non-B DNA structures in mammalian genomes. DNA Topoisomerase I (Top1) is often thought to regulate R-loop formation owing to its ability to resolve both positive and negative supercoils. How Top1 regulates R-loop structures at a global level is unknown. Here, we perform high-resolution strand-specific R-loop mapping in human cells depleted for Top1 and find that Top1 depletion results in both R-loop gains and losses at thousands of transcribed loci, delineating two distinct gene classes. R-loop gains are characteristic for long, highly transcribed, genes located in gene-poor regions anchored to Lamin B1 domains and in proximity to H3K9me3-marked heterochromatic patches. R-loop losses, by contrast, occur in gene-rich regions overlapping H3K27me3-marked active replication initiation regions. Interestingly, Top1 depletion coincides with a block of the cell cycle in G0/G1 phase and a trend towards replication delay. Our findings reveal new properties of Top1 in regulating R-loop homeostasis in a context-dependent manner and suggest a potential role for Top1 in modulating the replication process via R-loop formation. |
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