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Capture Hi-C Sequencing Service: Pinpoint Chromatin Interactions with Ultra-High Resolution

Move beyond the blur of whole-genome maps. Zoom in on the regulatory interactions that drive phenotype.

Standard Hi-C provides a global view of the 3D genome but often lacks the sequencing depth to resolve fine-scale regulatory loops without incurring prohibitive costs. CD Genomics bridges this gap with our Capture Hi-C Sequencing (CHi-C) Service. By combining in situ chromatin conformation capture with hybridization-based target enrichment, we achieve 1-2kb resolution at specific loci of interest.

Whether you are validating Enhancer-Promoter interactions, decoding the mechanism of GWAS risk variants, or mapping the Promoter Interactome, our targeted approach delivers crystal-clear data at a fraction of the cost of whole-genome sequencing.

  • Ultra-High Resolution: Detect fine-scale chromatin loops (1-2kb) inaccessible to standard Hi-C.
  • Cost-Efficiency: Generate high-depth, publication-ready maps with only 10-50 Gb of data per sample.
  • Flexible Customization: Target anywhere from a specific gene panel (dozens of loci) to the entire exome or promoter set (>20,000 probes).
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Capture Hi-C zooming in on specific chromatin loops with ultra-high resolution

Overview: The "Microscope" for 3D Genomics

From Global Structure to Fine-Scale Regulation

For the past decade, Hi-C sequencing has been the gold standard for mapping the global 3D architecture of the genome, successfully revealing hierarchical structures like A/B Compartments and Topologically Associating Domains (TADs). However, researchers often face a "Resolution vs. Cost" dilemma: resolving functional regulatory elements—such as specific Enhancer-Promoter (E-P) loops which are typically 5-10kb or smaller—requires billions of reads per sample using standard Hi-C. This makes the technology scalable only for detecting large structural features, often leaving the fine-scale regulatory wiring "blurry" or undetected.

Capture Hi-C (also known as Capture-C or CHi-C) acts as a high-precision microscope for the 3D genome. This technology integrates the proximity ligation chemistry of Hi-C with Solution Hybrid Selection (SHS) technology. By utilizing a pool of custom-designed, biotinylated RNA baits (probes) to specifically hybridize and pull down DNA fragments from regions of interest, we can enrich the targeted interactions by 100-fold to 1000-fold.

This enrichment strategy transforms the economics and resolution of 3D genomics. It allows researchers to:

  1. Validate hypothesized interactions with statistical rigor.
  2. Link non-coding variants (such as SNPs identified in GWAS) to their distal target genes, providing a physical mechanism for disease susceptibility.
  3. Map the complete regulatory landscape of specific gene families or pathways without sequencing the vast, uninformative intergenic deserts of the genome.

Technical Comparison: Capture Hi-C vs. Standard Hi-C

Feature Standard Hi-C (In Situ) Capture Hi-C
Primary Scope Global (Whole Genome Discovery) Targeted (Hypothesis Validation)
Resolution 10–40 kb 1–2 kb (Ultra-High / Promoter-Level)
Sequencing Data Required >100-300 Gb (High Cost) 10–50 Gb (Low Cost)
Enrichment Factor 1x (No enrichment) >100x (Target regions enriched)
Loop Detection Sensitivity Low for short/weak loops High for fine-scale regulatory loops
Best Use Case TAD calling, A/B Compartments, Genome Scaffolding Enhancer-Promoter linking, GWAS mechanism, CRISPR off-target analysis

Service Portfolio: Targeted Solutions

We offer two distinct service tracks for Capture Hi-C, powered by our proprietary probe design algorithms that utilize "Bait Tiling" strategies to maximize capture efficiency and minimize off-target noise.

1. Promoter Capture Hi-C (PCHi-C)

Mapping the "Promoter Interactome" Gene expression is largely driven by physical contacts between promoters and distal regulatory elements (enhancers, silencers). Our Promoter Capture Hi-C service utilizes a standardized, highly optimized probe library designed to target all annotated gene promoters in the genome (e.g., targeting ~22,000 promoters in the human genome).

  • Design Strategy: We target the restriction fragments (e.g., HindIII or DpnII fragments) containing transcriptional start sites (TSS).
  • Application: Ideal for constructing a global "Promoter Interactome," identifying all distal enhancers regulating every coding gene in a specific cell type or tissue. This is the method of choice for characterizing the regulatory landscape of a new cell line or developmental stage.

2. Custom Capture Hi-C

Bespoke Precision for Specific Hypotheses For researchers focusing on specific biological questions, we offer a fully customizable capture service. You provide the genomic coordinates (BED file) or gene names, and we design a tailored probe panel. Target scope can range from a few kilobases to hundreds of megabases.

  • GWAS Variant Panels: Target regions harboring disease-associated SNPs to identify their physical target genes (which are often distinct from the nearest linear gene).
  • Super-Enhancer Capture: Specifically map the interaction networks of super-enhancers to understand cell-identity regulation.
  • Breakpoint & Integration Site Capture: Design probes flanking chromosomal translocation breakpoints or viral integration sites (e.g., HPV, HBV) to study how these events remodel local 3D chromatin structure.
  • Gene Pathway Panels: Focus on specific gene families (e.g., Hox genes, immune receptors) to study their co-regulation mechanisms.

Applications

Biomedical Research: Decoding GWAS & Disease Mechanisms

The vast majority (>90%) of disease-associated genetic variants (SNPs) identified by Genome-Wide Association Studies (GWAS) are located in non-coding regions. The "nearest gene" assignment method is often incorrect. Capture Hi-C provides the definitive physical link connecting these non-coding SNPs to their distal target genes, often skipping over multiple intervening genes. This is critical for translating GWAS findings into actionable therapeutic targets in oncology, immunology, and metabolic diseases.

Evolutionary Biology: Comparative 3D Genomics

Regulatory elements often evolve faster than coding sequences. By using Capture Hi-C probes designed for conserved regions (or species-specific variants), researchers can compare the 3D regulatory architecture of specific elements—such as Human Accelerated Regions (HARs)—across species (e.g., Human vs. Chimpanzee). This reveals how changes in chromatin folding contribute to species-specific traits and brain evolution.

Agricultural Biotechnology (AgBio)

Crop genomes (e.g., Wheat, Maize, Sugarcane) are often massive, polyploid, and repetitive, making whole-genome Hi-C financially unsustainable for large populations. Capture Hi-C allows AgBio researchers to ignore the repetitive intergenic "junk" DNA and focus sequencing power solely on gene-rich regions or specific Quantitative Trait Loci (QTLs). This enables the cost-effective mapping of regulatory networks controlling traits like yield, drought resistance, and nutrient use efficiency.

Workflow: Precision Enrichment

Our Capture Hi-C workflow is a sophisticated two-stage process that integrates our robust In Situ Hi-C library preparation with high-efficiency Solution Hybrid Selection. We adhere to strict SOPs to ensure reproducibility and high enrichment efficiency.

Phase 1: Hi-C Library Construction (The Foundation)

Before capture, we must construct a high-quality 3D library.

Step 1: In Situ Crosslinking
Cells or tissues are fixed with 2% formaldehyde. Crucially, we perform this step in situ (inside the nucleus) to lock chromatin loops in their native conformation, preventing spurious ligation events.

Step 2: Chromatin Digestion
The crosslinked chromatin is digested with a specific restriction enzyme (typically HindIII or DpnII). The choice of enzyme determines the theoretical resolution limit; 4-base cutters (DpnII) offer higher resolution than 6-base cutters (HindIII).

Step 3: Biotin Fill-in & Proximity Ligation
The resulting "sticky ends" of DNA are filled in with biotinylated nucleotides. Ligase is added under extremely dilute conditions to favor intramolecular ligation—joining two DNA ends that are physically close in 3D space, even if they are distant in linear sequence.

Step 4: DNA Purification & Shearing
Crosslinks are reversed, proteins are degraded, and pure DNA is extracted. The DNA is then sheared (using Covaris ultrasonication) to a uniform fragment size (300-500bp).

Phase 2: Target Enrichment (The "Capture")

This is where the magic happens. We use custom probes to fish out the interactions of interest.

Step 5: Probe Design & Synthesis
Using our proprietary "Bait Tiling" algorithm, we design 120bp biotinylated RNA baits. We tile probes across the target restriction fragments (e.g., 2 baits per fragment end) to ensure robust capture even if one probe site is mutated or masked by repeats.

Step 6: Hybridization
The Hi-C library is denatured and hybridized with the RNA bait library. This step is optimized for thermodynamics (temperature and duration) to ensure specific binding between the RNA probes and the target DNA sequences (including the chimeric ligation junctions containing the "prey" DNA).

Step 7: Streptavidin Pull-Down
Magnetic Streptavidin beads are added to bind the Biotinylated RNA-DNA hybrids.

Step 8: Stringent Washing
We perform a series of rigorous washes at specific temperatures to remove off-target DNA and non-specific binding, ensuring that only the targeted interactions remain.

Step 9: PCR Amplification & Sequencing
The enriched library is amplified and sequenced on Illumina NovaSeq platforms (PE150 mode). We typically target 10-50 Gb of raw data, depending on the panel size.

Capture Hi-C Workflow Diagram

Why Choose CD Genomics

We are dedicated to providing the highest quality 3D genomics services to accelerate your research.

Proprietary Probe Design Algorithms

We handle the complex bioinformatics of probe design. Our "Bait Tiling" and "Repeat Masking" strategies ensure maximum capture efficiency (>70% on-target rate) and minimal off-target effects, even in complex genomes.

Sample Versatility

From precious clinical biopsies (low input) to recalcitrant plant tissues rich in polyphenols, our optimized extraction and fixation protocols ensure successful library construction from diverse and challenging sample types.

End-to-End Support

We provide a truly seamless workflow. You simply provide a gene list or BED file; we handle everything from probe synthesis and library prep to sequencing and publication-ready bioinformatic analysis.

Cost-Effective Customization

We tailor the sequencing depth and target size to your specific budget. By focusing only on what matters, we help you save up to 80% on sequencing costs compared to WGS Hi-C.

Sample Requirement Specifications

To ensure the success of the Capture Hi-C assay, high-quality starting material is essential. Please adhere to the following guidelines.

Sample Type Recommended Input Minimum Input Preparation & Storage
Cultured Cells 1×107 cells 2×106 cells Fresh: Pellet and flash freeze.
Fixed: 2% Formaldehyde for 10 min.
Animal Tissue 500 mg 100 mg Rinse with saline, remove fat/connective tissue, cut into small pieces (<0.5cm), flash freeze.
Plant Tissue 2 g 1 g Select young, tender leaves. Wash surface dirt, cut into pieces, flash freeze.
Blood/Fluid 5-10 mL 2 mL Collect in EDTA (purple top) tubes.

Shipping Instructions: All samples must be shipped on dry ice (>5kg). Use screw-cap cryotubes to prevent leakage.

Comprehensive Bioinformatic Analysis

Our bioinformatics pipeline is specifically tuned for Capture Hi-C data, utilizing specialized algorithms (like CHiCAGO or GotHiC) to handle the non-uniform coverage inherent to enrichment data.

Module Specific Analysis Items Description & Key Deliverables
1. Standard Processing QC & Mapping • Raw data quality control (FastQC).
• Mapping to reference genome (Bowtie2).
• Capture Efficiency Statistics (On-target vs. Off-target rates).
• Filtering of invalid pairs (self-circles, dangling ends).
2. Structural Analysis Interaction Calling • Generation of high-resolution contact matrices (1kb, 5kb bins).
• Significant Loop Calling: Identification of high-confidence interactions (P-value < 0.01) using background models appropriate for capture data (e.g., CHiCAGO).
3. Visualization Virtual 4C & Heatmaps • Targeted Heatmaps: Visualization of the interaction matrix at captured loci.
• Virtual 4C Plots: Profiles showing interaction frequency from a specific "viewpoint" (e.g., a promoter) to the rest of the genome.
4. Integrative Analysis Multi-Omics Overlay • Integration with ChIP-seq (H3K27ac, CTCF) and ATAC-seq tracks to annotate the regulatory nature of loops (e.g., Active Enhancer-Promoter loops).
• Correlation with RNA-seq gene expression.
5. Custom Analysis Comparative & GWAS • Differential Loop Analysis: Identifying loops that are significantly strengthened or lost between conditions (e.g., Case vs. Control).
• GWAS Linking: Annotating SNPs located in loop anchors to link risk variants to target genes.

Demo Results

Visualize regulatory connections with clarity:

  • Targeted Interaction Heatmaps: Crystal-clear visualization of chromatin interactions at your regions of interest, free from whole-genome noise.
  • Differential Loop Tables: Quantitative lists of loops that change strength between experimental conditions (e.g., Wild-type vs. Mutant).
  • Virtual 4C Plots: Profiles showing interaction frequency from a specific "viewpoint" (e.g., a promoter) to the rest of the genome, mimicking 4C-seq data but derived from the capture dataset.
  • Multi-Omics Tracks: Overlays of Capture Hi-C arcs with histone marks (ChIP-seq) and open chromatin signals (ATAC-seq) to validate functional connections.

Comparison of Standard Hi-C vs Capture Hi-C interaction heatmaps showing enrichment efficiencyEnrichment Efficacy (Before vs. After)

Virtual 4C plot showing promoter-enhancer interactions peaks.Virtual 4C Viewpoint Analysis

Arc diagrams showing differential chromatin loops between Wild-type and Mutant samples.Differential Loop Analysis

Integration of Capture Hi-C loops with GWAS SNP tracks linking variants to genes.GWAS SNP-Gene Association

Case Study: High-Resolution Chromatin Landscape Reveals Transcriptional Dynamics in Plants

Plants, as sessile organisms, must rapidly adjust their gene expression to survive environmental stresses like cold. While chromatin architecture is known to influence transcription, standard Hi-C methods often lack the spatial resolution to visualize fine-scale interactions within gene bodies or between closely spaced promoters. This study aimed to use a high-resolution capture-based approach (CAP-C, a variant similar to Capture Hi-C) to map the 3D chromatin landscape of Arabidopsis thaliana and determine how chromatin conformation dynamically rewires during cold stress response.

The researchers employed a high-resolution chromatin capture technology to achieve sub-kilobase (sub-kb) resolution, focusing on gene-rich regions. This structural data was integrated with RNA Polymerase II (Pol II) ChIP-seq and RNA-seq data. The goal was to correlate physical chromatin loops with transcriptional machinery occupancy and gene expression levels under both normal growth conditions and cold-stress treatment.

Figure 1. Fine-scale chromatin interactions regulate transcription.

The high-resolution contact map reveals specific chromatin loops connecting the transcription start site (TSS) with the termination site (TTS), known as "gene loops." Under cold stress, these local chromatin interactions rewire dynamically, showing a strong correlation with changes in Pol II activity.

The high-resolution maps revealed unprecedented details of the plant 3D genome. Unlike standard Hi-C, which primarily defines large TADs, this approach identified fine-scale chromatin loops within gene bodies and between promoters. Crucially, the study found significant dynamic changes in local chromatin interactions upon cold treatment. These structural changes facilitated a "Promoter-Promoter Interaction (PPI) network," allowing co-regulated genes to cluster spatially for synchronized expression during stress.

This study demonstrates the power of High-Resolution Capture interactions in decoding complex regulatory mechanisms. By zooming in to the sub-kb level, researchers proved that chromatin conformation is not static but dynamically rewires to orchestrate transcriptional responses to environmental stress. This validates Capture Hi-C's capability to link fine-scale 3D structure to phenotype, a critical tool for advancing agricultural biotechnology and crop resilience research.

Frequently Asked Questions

References

  1. Zhang, Y., et al. "A fine-scale Arabidopsis chromatin landscape reveals chromatin conformation-associated transcriptional dynamics." Nature Communications 15, 3253 (2024).
  2. Mifsud, B., et al. "Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C." Nature Genetics 47, 598–606 (2015).
  3. Javierre, B.M., et al. "Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters." Cell 167, 1369–1384 (2016).
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High-confidence 3D genomics services for chromatin interaction analysis and regulatory insight.

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