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

Stefano G. Manzo, Stella R. Hartono, Lionel A. Sanz, Jessica Marinello, Sara De Biasi, Andrea Cossarizza, Giovanni Capranico, Frederic Chedin

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Background: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Article number100
JournalGenome Biology
Volume19
Issue number1
DOIs
StatePublished - Jul 30 2018

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology

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    Manzo, S. G., Hartono, S. R., Sanz, L. A., Marinello, J., De Biasi, S., Cossarizza, A., Capranico, G., & Chedin, F. (2018). DNA Topoisomerase I differentially modulates R-loops across the human genome. Genome Biology, 19(1), [100]. https://doi.org/10.1186/s13059-018-1478-1