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DNA Topoisomerase I differentially modulates R loop across long genes and at human replication origins

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 performed high-resolution strand-specific R-loop mapping in human cells depleted for Top1 and found that Top1 depletion resulted in both R-loop gains and losses at thousands of transcribed loci, delineating two distinct gene classes. R-loop gains were 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, occurred in gene-rich regions overlapping H3K27me3-marked active replication origins. Interestingly, Top1 depletion coincided with a block of the cell cycle in G0/G1 phase and a trend towards global replication delay. Our findings reveal new properties of Top1 in regulating R-loop homeostasis and suggest a potential role for Top1 in controlling replication origin via R-loop formation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE102474 | GEO | 2018/06/26

REPOSITORIES: GEO

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