What is the difference between iMARGI and GRID-seq?

Both are all-to-all mapping methods, but they differ in their ligation chemistry. iMARGI typically utilizes a simpler ligation protocol that is highly efficient for nascent RNA, while GRID-seq uses a specialized bivalent linker that can provide very high specificity for stable chromatin-associated RNAs.

When should I choose DRIP-seq over MapR for R-loop detection?

DRIP-seq is the most widely cited method and is excellent for broad surveys of R-loop hotspots. However, if you have very limited cells, MapR or CUT&Tag-R-loop provide a much higher signal-to-noise ratio with significantly less starting material.

Can these services detect both cis and trans RNA-DNA interactions?

Yes. All-to-all methods like iMARGI and RADICL-seq are designed to capture the full interactome, including cis interactions (regulation at the site of synthesis) and trans interactions (regulation at distal chromosomes).

Global RNA-Chromatin Interaction Mapping Services

Explore the intricate regulatory landscape of the nucleus with our Global RNA-Chromatin Interaction Mapping Services. From unbiased, all-to-all RNA-DNA profiling using iMARGI and GRID-seq to high-resolution R-loop sequencing via DRIP-seq and MapR, we offer a total solution for studying chromatin-associated RNAs and genomic stability. Map the RNA-DNA interactome with unprecedented precision. RUO.

Unbiased Mapping: All-to-all detection via iMARGI and GRID-seq.
R-loop Expertise: Full suite of DRIP-seq, MapR, and CUT&Tag-R-loop.
High Sensitivity: Optimized protocols for low-input samples.
Comprehensive Analysis: Bioinformatic pipelines for integrative epigenomics.

Overview: Uncovering the Functional Interface of RNA and DNA

The regulation of the genome is no longer viewed as a protein-only process. Recent breakthroughs have revealed that the "RNA-DNA interactome"—the complex network of associations between various RNA species and the chromatin fiber—plays a fundamental role in epigenetic inheritance, X-chromosome inactivation, and genomic stability.

Our Global RNA-Chromatin Interaction Mapping Services provide a comprehensive toolkit to bridge the gap between the transcriptome and the epigenome. We offer specialized technologies to map the attachment of long non-coding RNAs (lncRNAs), small nuclear RNAs (snRNAs), and nascent transcripts to the genome across the entire 3D nuclear space. Additionally, we provide high-sensitivity detection for R-loops (DNA:RNA hybrids), which are critical indicators of transcription-induced genomic stress.

By mapping these interactions, researchers can gain a mechanistic understanding of how non-coding RNAs act as functional scaffolds or guides for chromatin remodeling complexes. This visual and digital evidence is essential for defining the next generation of genomic regulation models.

Diagram of RNA strands interacting with a DNA double helix forming R-loop structures.

RNA-DNA All-to-All Interaction Mapping (NGS-based)

For researchers seeking to understand the global distribution of chromatin-associated RNAs (caRNAs), we provide several "all-to-all" mapping technologies. These methods capture the global landscape of RNA-DNA interactions without requiring a specific protein or RNA "bait."

iMARGI

iMARGI (In Situ Mapping of RNA-Genome Interactions) is the leading method for unbiased, all-to-all mapping. It converts RNA-DNA proximal associations into chimeric cDNA sequences. Because it captures interactions in an in situ manner, it preserves the spatial context of how nascent and regulatory RNAs interact with distal genomic loci.

GRID-seq & ChAR-seq

Both GRID-seq (Global RNA-Interactions-with-DNA sequencing) and ChAR-seq (Chromatin-Associated RNA sequencing) utilize bivalent linkers to ligate chromatin-associated RNA to neighboring genomic DNA. These methods are highly effective at capturing both cis and trans interactions globally.

RADICL-seq

RADICL-seq offers an optimized workflow that increases the efficiency of RNA-DNA ligation while reducing background noise. It is particularly useful for studying how RNA-DNA interactions change across different cell states or experimental treatments.

Specialized R-loop Sequencing & Detection

R-loops are three-stranded structures consisting of a DNA:RNA hybrid and a displaced single strand of DNA. While they have biological functions, their accumulation is a major source of DNA damage. We provide multiple methods to profile these structures genome-wide.

DRIP-seq & DRIPc-seq

DNA-RNA Immunoprecipitation Sequencing (DRIP-seq) is the established standard for R-loop profiling, utilizing the S9.6 antibody. DRIPc-seq adds a stranded-sequencing component, allowing for the precise identification of which DNA strand the RNA is hybridized to.

MapR & CUT&Tag-R-loop

For researchers with limited sample material, we offer enzyme-based alternatives. MapR and CUT&Tag-R-loop utilize modified RNase H to target and release R-loop-associated DNA fragments with high sensitivity.

Technical Workflow: From Ligation to Interaction Maps

All global RNA-chromatin mapping services follow a rigorous molecular biology pipeline designed to ensure the fidelity of the RNA-DNA chimeric molecule. While specific chemistries vary, the core process includes:

Nuclei Preparation & Fixation: Samples are crosslinked to preserve native spatial associations between RNA and the chromatin fiber.
Chromatin Digestion: Genomic DNA is fragmented using restriction enzymes or sonication to generate accessible ends for ligation.
Proximity Ligation: RNA ends are ligated to proximal DNA ends, either directly (iMARGI) or via a bivalent linker (GRID-seq/RADICL-seq).
Chimera Purification: Non-ligated molecules are removed, and chimeric RNA-DNA molecules are purified via biotin-streptavidin pull-down.
Library Prep & Sequencing: Chimeras are converted into NGS libraries and sequenced on Illumina platforms.
Bioinformatic Analysis: Reads are split, mapped to the reference genome, and interaction matrices are generated for visualization.

Research Applications & Biological Significance

Global RNA-chromatin mapping is an essential tool for understanding the "hidden" layer of gene regulation. Our services empower research in several key areas:

Regulation of Chromatin State by lncRNAs: Identify exactly where regulatory RNAs dock to recruit chromatin modifiers like PRC2.
X-Chromosome Inactivation: Study the spreading of Xist and other non-coding RNAs across chromosomes during development.
Genomic Instability & R-loop Dynamics: Identify fragile sites where RNA:DNA hybrids interfere with replication, leading to DNA damage in cancer.
Transcription-Induced 3D Reorganization: Analyze how nascent RNAs influence local 3D architecture and transcriptional factory formation.

Comparison: Choosing Your RNA-Chromatin Method

Selecting the right method depends on whether you want to map regulatory RNAs or investigate genomic stability via R-loops. Compare our primary technologies below:

Method Category	Key Technologies	Primary Goal	Input Requirement
All-to-All Mapping	iMARGI, GRID-seq, RADICL-seq	Map all caRNAs to the genome	Standard (High)
Antibody-Based R-loop	DRIP-seq, DRIPc-seq	Gold-standard R-loop enrichment (S9.6)	Standard
Enzyme-Based R-loop	MapR, CUT&Tag-R-loop	High-resolution, low-input detection	Ultra-Low
Protein-Centric	R-ChIP	Mapping RNase H1 occupancy sites	Moderate

Comparison chart for selecting RNA-Chromatin sequencing services based on goal and input.