Prevalent, Dynamic, and Conserved R-Loop Structures Associate with Specific Epigenomic Signatures in Mammals

Area of Science:

• Molecular Biology
• Genomics
• Epigenetics

Background:

• R-loops are three-stranded nucleic acid structures (RNA:DNA hybrids).
• Their genome-wide prevalence and functional roles in mammals remain incompletely understood.

Purpose of the Study:

• To profile R-loops with high resolution and strand specificity in human and mouse cells.
• To investigate the association of R-loops with chromatin states and gene regulatory elements.

Main Methods:

• High-resolution, strand-specific R-loop profiling.
• Epigenomic profiling (e.g., chromatin accessibility, DNA methylation).

Main Results:

• R-loops occupy up to 5% of mammalian genomes, primarily at promoter and terminator regions.
• R-loops form co-transcriptionally with dynamic turnover.
• Promoter R-loops associate with accessible, unmethylated CpG island chromatin.
• Terminal R-loops correlate with enhancer/insulator-like states and define transcription terminators.

Conclusions:

• R-loops are abundant, dynamic components of mammalian chromatin.
• Nascent RNA retention in R-loops influences chromatin patterning and gene expression control.