DNA Topoisomerase I differentially modulates R-loops across the human genome
DNA Replication
0301 basic medicine
570
Chromatin Immunoprecipitation
Transcription, Genetic
Bioinformatics
QH301-705.5
1.1 Normal biological development and functioning
Type I
QH426-470
Small Interfering
Resting Phase, Cell Cycle
Histones
03 medical and health sciences
Genetic
Underpinning research
Information and Computing Sciences
Heterochromatin
Genetics
Humans
Gene Silencing
Biology (General)
RNA, Small Interfering
0303 health sciences
Genome
Chromatin Immunoprecipitation; DNA; DNA Replication; DNA Topoisomerases, Type I; G1 Phase Cell Cycle Checkpoints; Gene Silencing; HEK293 Cells; Heterochromatin; Histones; Humans; Lamin Type B; Nucleic Acid Conformation; RNA Polymerase II; RNA, Small Interfering; Resting Phase, Cell Cycle; Genome, Human; Transcription, Genetic; Ecology, Evolution, Behavior and Systematics; Genetics; Cell Biology
Lamin Type B
Genome, Human
Research
Cell Cycle
DNA
Biological Sciences
G1 Phase Cell Cycle Checkpoints
Chromatin Immunoprecipitation; DNA; DNA Replication; DNA Topoisomerases, Type I; G1 Phase Cell Cycle Checkpoints; Gene Silencing; HEK293 Cells; Heterochromatin; Histones; Humans; Lamin Type B; Nucleic Acid Conformation; RNA Polymerase II; RNA, Small Interfering; Resting Phase, Cell Cycle; Genome, Human; Transcription, Genetic
HEK293 Cells
DNA Topoisomerases, Type I
RNA
Resting Phase
Nucleic Acid Conformation
Generic health relevance
RNA Polymerase II
Transcription
DNA Topoisomerases
Environmental Sciences
Human
DOI:
10.1186/s13059-018-1478-1
Publication Date:
2018-07-30T11:17:28Z
AUTHORS (8)
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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CITATIONS (128)
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