HiChIP Sequencing Service for Targeted 3D Genome Interaction Mapping
Uncover enhancer–promoter loops and protein-mediated chromatin architecture with high sensitivity, low input, and publication-ready insights.
CD Genomics provides HiChIP sequencing services to help researchers map protein-guided chromatin interactions in 3D. By combining ChIP-seq and Hi-C, HiChIP enables high-resolution detection of enhancer–promoter loops and regulatory domains with low input and high specificity. Our optimized workflow and expert analysis offer a powerful solution for studying transcription factor binding, histone modifications, and long-range gene regulation.
Key features:
- Protein-specific chromatin loop detection
- Low input requirements, high signal-to-noise ratio
- Optimized for transcription factors, histone marks, super-enhancers
- Fast, scalable, and fully supported by expert bioinformatics
Why Choose HiChIP? A Focused 3D Lens
Understanding how chromatin folds in space is essential to interpreting the regulatory logic of the genome. While Hi-C offers a comprehensive overview of genome architecture, it captures all interactions—regardless of function or relevance. ChIP-seq, in contrast, provides high-resolution maps of protein binding, but lacks spatial context. Neither alone can reveal how specific regulatory proteins orchestrate long-range chromatin communication.
HiChIP was developed to close this gap.
By combining spatial DNA interaction capture with chromatin immunoprecipitation, HiChIP enables precise mapping of protein-mediated chromatin loops—such as enhancer–promoter interactions—within their native 3D context. It doesn't just show you where your protein binds; it reveals which genomic regions it brings together, and how these interactions shape transcriptional programs.
From a research perspective, HiChIP offers several clear advantages:
- Functionally Anchored Interaction Maps
HiChIP enriches for interactions mediated by your protein of interest, avoiding the data overload and interpretation challenges common in untargeted Hi-C datasets.
- Reduced Input, Increased Insight
Thanks to selective pull-down and optimized library prep, HiChIP delivers high-resolution results from limited material—particularly useful for rare cell populations or precious samples.
- Improved Signal-to-Noise Ratio
Focused enrichment of biologically relevant contacts enables clearer identification of loops and regulatory hubs, improving data interpretability and downstream analysis.
- Versatility Across Research Models
Whether you're studying transcription factor networks, chromatin boundary elements, or epigenetic modifications, HiChIP adapts well to diverse experimental systems and target proteins.
HiChIP doesn't aim to replace Hi-C or ChIP-seq—it integrates the strengths of both to answer questions neither can resolve alone. If your research demands spatial resolution and molecular specificity, HiChIP offers a uniquely informative window into chromatin structure and function.
Streamlined Workflow: Science, Not Guesswork
HiChIP features an optimized workflow that converts complex chromatin interaction data into actionable insights with high precision. Combining the strengths of ChIP-seq (targeted enrichment) and Hi-C (spatial interaction analysis), it provides reliable, high-resolution interaction maps while avoiding the complexity and noise of traditional methods.
Our process prioritizes accuracy, efficiency, and minimal sample loss, delivering clean, biologically meaningful results. Here's how it works:
Step 1: In Situ Crosslinking
The process starts with in situ crosslinking of nuclear DNA and proteins, stabilizing their interactions to preserve the native chromatin structure and spatial relationships—minimizing non-specific binding or degradation in subsequent steps.
Step 2: Ligation and Biotin Labeling
Crosslinked chromatin undergoes spatial DNA interaction capture, covalently joining interacting DNA regions. Biotin labeling is incorporated during ligation to enable specific capture of these ligated fragments later, ensuring focus on biologically relevant interactions mediated by the target protein/modification.
Step 3: Chromatin Immunoprecipitation (ChIP)
Chromatin is sheared into small fragments via sonication, followed by immunoprecipitation using an antibody against the target protein/modification. This enriches for chromatin regions directly bound/regulated by the target, narrowing the focus to relevant interactions and ensuring data specificity.
Step 4: Library Preparation and Sequencing
Biotin-labeled fragments are captured and processed into libraries using Tn5 transposase-based tagmentation (for efficient adapter integration), then sequenced on the NovaSeq 6000 platform. The result is a clean, high-quality dataset ready for in-depth analysis.
Key Workflow Benefits
High Sensitivity with Low Input: Enriched profiles enable high-resolution data from small/rare samples, addressing a major limitation of traditional methods.
Targeted Precision: Selective enrichment eliminates background noise, ensuring data reflects genuine, functional chromatin interactions.
Versatile Applications: Suitable for studying gene regulation, epigenetic modifications, enhancer-promoter interactions, and more—adapting to diverse research needs.
By merging advanced technologies with a streamlined, research-centric workflow, HiChIP delivers high-quality data that reliably represents real, functional genomic interactions—giving researchers confidence in their results.
Technical Strengths That Matter
HiChIP combines precision, efficiency, and reliability to address challenges researchers face when mapping chromatin interactions. By refining traditional methods, HiChIP offers a powerful solution for studying protein-mediated chromatin loops.
1. High Specificity, Low Noise
HiChIP targets interactions mediated by the protein or histone modification of interest, reducing the background noise found in broader methods like Hi-C. This selective enrichment ensures cleaner, more interpretable data, improving the accuracy of chromatin loop identification.
2. Efficient Use of Minimal Material
HiChIP requires less input material than Hi-C or ChIA-PET, making it ideal for rare or small samples. Whether working with primary cells, stem cells, or biopsies, HiChIP can generate high-quality data from limited material, reducing the need for large cell populations.
3. Streamlined Protocols for Faster Results
HiChIP's optimized library preparation and spatial DNA interaction capture protocols reduce the time required to prepare sequencing-ready libraries. The streamlined workflow enhances efficiency, saving time and minimizing variability, while delivering reproducible results.
4. Protein-Centric Interaction Mapping
HiChIP focuses on protein-mediated chromatin interactions, providing insights into how transcription factors or histone modifications shape chromatin architecture. This protein-centric approach allows precise mapping of enhancer–promoter interactions and regulatory hubs.
5. Enhanced Data Quality and Interpretation
By focusing on relevant interactions, HiChIP provides higher-resolution, more interpretable data compared to untargeted approaches. This makes it a powerful tool for understanding chromatin structure and gene regulation.
6. Versatile Applications Across Research Models
HiChIP is adaptable to a range of biological systems, including cancer models, stem cells, and in vivo studies. Whether studying gene regulation, epigenetic modifications, or chromatin dynamics, HiChIP delivers reliable, high-quality data for diverse research needs.
HiChIP combines specificity, efficiency, and streamlined workflows to provide researchers with clear, actionable insights into chromatin interactions.
Choosing the Right 3D Genomics Tool: How HiChIP Stands Apart
Selecting the right tool for mapping chromatin interactions is critical for the success of your research. HiChIP, Hi-C, ChIA-PET, and PLAC-seq each offer unique strengths. Below is a comparative table to help you choose the right approach based on your specific research needs.
| Feature | Hi-C | ChIA-PET | PLAC-seq | HiChIP |
|---|---|---|---|---|
| Type of Interactions | Genome-wide 3D interactions | Protein-specific long-range interactions | Protein-specific long-range interactions | Protein-specific chromatin loops |
| Specificity | Low (untargeted) | High (specific protein) | High (specific protein) | Very High (targeted protein/mark) |
| Input Requirements | High (millions of cells) | Very high (large amounts of material) | Medium (requires good quality input) | Low (can work with fewer cells) |
| Data Complexity | High (complex, noisy) | Medium (requires careful interpretation) | Medium (good for targeted analysis) | Low (focused on relevant interactions) |
| Resolution | Medium to low | High | High | Very High (precise loop mapping) |
| Cost | High | High | Medium | Medium |
| Workflow Complexity | Complex (long, multi-step process) | Complex (requires more steps) | Moderate (fewer steps than ChIA-PET) | Streamlined (simplified steps) |
| Data Output | Genome-wide maps of interactions | Protein-centric interaction data | Protein-centric interaction data | Protein-centric loop data |
| Best For | Broad, untargeted chromatin interaction mapping | Specific protein binding and long-range interactions | Targeted protein-specific interactions | Targeted, high-resolution chromatin loop mapping |
| Key Advantage | Provides a global view of chromatin structure | Can link protein interactions to distant regulatory elements | Similar to HiChIP but uses a different library prep | High specificity, low background, and can be used with small samples |
Bioinformatics Tailored to Your Hypothesis
HiChIP sequencing data is processed with comprehensive bioinformatics support to provide tailored insights into your research. Key steps include:
- Sequence alignment
- Quality control (QC) analysis
- HiChIP interaction heatmaps (500 kb, 25 kb, 5 kb resolution)
- Loop calling
- Loop annotation
- Loop-related peak identification
- Loop visualization
- Differential loop analysis
- Transcription factor motif analysis
- Differential loop-related gene GO analysis
- Differential loop-related gene KEGG pathway analysis
- Virtual 4C visualization
Sample Visual Data Outputs:
- Loop visualizations
- Loop length histograms
- Loop distance histograms
- Interaction significance plots
- Loop MA plots
- Contact filtering plots
- Loop volcano plots
- Box and violin plots
Key Research Applications for HiChIP Sequencing
Transcription factors (TFs) are proteins that control the expression of genes by binding to specific regions of DNA. HiChIP helps researchers map the 3D interactions between these factors and their target genes. This allows scientists to:
- Identify how transcription factors regulate gene expression
- Understand the role of TFs in development, disease, and stress responses
- Discover key regulatory hubs and networks within the genome
Enhancers are regulatory DNA elements that control gene expression by interacting with promoters. HiChIP enables precise mapping of these enhancer–promoter loops in three dimensions. This helps researchers:
- Investigate how enhancers and promoters communicate to drive gene activation
- Study how changes in these interactions influence diseases such as cancer
- Discover new enhancer–promoter interactions that drive cellular differentiation
Chromatin architecture plays a critical role in regulating gene expression by organizing the genome into functional domains. HiChIP helps map the 3D structure of chromatin, providing insights into how epigenetic modifications such as histone modifications shape genome organization. This helps researchers:
- Understand how chromatin folding influences gene activation and repression
- Investigate how epigenetic marks contribute to disease development
- Reveal how the spatial arrangement of chromatin impacts gene regulation
Super-enhancers are large clusters of enhancers that control the expression of key genes. HiChIP helps identify long-range interactions between super-enhancers and target genes, offering valuable insights into gene regulation. This helps researchers:
- Map the role of super-enhancers in cellular identity and disease
- Understand how super-enhancers coordinate gene expression in response to stimuli
- Investigate how super-enhancers contribute to disease-driving genes in cancer
What We Require from You
To ensure the success of your HiChIP project, we require high-quality samples and proper preparation. Please follow the guidelines below:
Sample Preparation
- Fixed Cells: If your samples have been cross-linked, please provide cell pellets that have been properly fixed.
- Shipping: Ship fixed cells on dry ice.
- Note: Contact us for guidance on cross-linking protocols if needed.
- Live Cells: If fixed cells are not available, you may submit live cells along with the appropriate culture media for transport.
- Shipping: Live cells should be shipped at room temperature.
- Additional Costs: If cell pre-treatment is required (e.g., cross-linking, cell culture), please provide detailed instructions and materials. Additional fees may apply based on sample preparation.
Sample Requirements
- Sample Type: Fixed or live cells
- Cell Quantity: At least 1.5 × 10⁷ cells per sample
- Species: Human, mouse, or rat (other species may be considered upon request)
How It Works: From Bench to Data
Sequencing strategy:
