DNA Topoisomerase I differentially modulates R-loops across the human genome

• DOI: 10.1186/s13059-018-1478-1
• Publication Date: 2018-07-30T11:17:28Z
• Authors: Stefano G. Manzo; Stella R. Hartono; Lionel A. Sanz; Jessica Marinello; Sara De Biasi; Andrea Cossarizza; Giovanni Capranico; Frederic Chedin
• Keywords: Replication timing; Origin recognition complex

Co-transcriptional R-loops are abundant non-B DNA structures in mammalian genomes. Topoisomerase I (Top1) is often thought to regulate R-loop formation owing its ability resolve both positive and negative supercoils. How Top1 regulates at a global level unknown. Here, we perform high-resolution strand-specific mapping human cells depleted for find that depletion results gains losses thousands of transcribed loci, delineating two distinct gene classes. characteristic long, highly transcribed, genes located gene-poor regions anchored Lamin B1 domains proximity H3K9me3-marked heterochromatic patches. losses, by contrast, occur gene-rich overlapping H3K27me3-marked active replication initiation regions. Interestingly, coincides with block the cell cycle G0/G1 phase trend towards delay. Our findings reveal new properties regulating homeostasis context-dependent manner suggest potential role modulating process via formation.