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Updated: Apr 22, 2026

CRISPR-Mediated Reorganization of Chromatin Loop Structure
Published on: September 14, 2018
R-loops induce repressive chromatin marks over mammalian gene terminators
Konstantina Skourti-Stathaki1, Kinga Kamieniarz-Gdula1, Nicholas J Proudfoot1
1Sir William Dunn School of Pathology, South Parks Road, University of Oxford, Oxford OX1 3RE, UK.
R-loops, DNA-RNA hybrids, induce antisense transcription at gene termination sites. This triggers RNA interference, leading to repressive histone marks that reinforce RNA polymerase II pausing and promote gene termination.
Area of Science:
- Molecular Biology
- Epigenetics
- Gene Regulation
Background:
- R-loops are DNA-RNA hybrids formed during transcription.
- Previously considered transcriptional byproducts, R-loops are now known to have regulatory roles.
- R-loops are enriched at G-rich terminator elements, influencing RNA polymerase II pausing.
Purpose of the Study:
- To investigate the functional role of R-loops at gene termination sites.
- To elucidate the mechanism linking R-loops to epigenetic modifications and transcriptional termination.
Main Methods:
- Analysis of R-loop formation and associated epigenetic marks.
- Investigating the role of RNA interference pathway components (DICER, AGOs).
- Studying the impact on RNA polymerase II pausing and gene termination.
Main Results:
- R-loops induce antisense transcription at pause elements.
- Antisense transcripts generate double-stranded RNA, recruiting DICER and AGO proteins.
- This leads to H3K9me2 deposition and HP1γ recruitment, reinforcing Pol II pausing.
Conclusions:
- R-loops promote RNA-interference-dependent H3K9me2 formation at termination regions.
- R-loops contribute to a chromatin architecture defining gene termination sites.
- This mechanism regulates transcriptional termination in mammalian protein-coding genes.
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