HiChIP Service: Unlock 3D Genome Interactions with Fast, Low-Input, High-Resolution

At CD Genomics, we bring years of hands-on experience in HiChIP assay development and optimisation. Our team has successfully delivered numerous high-quality HiChIP datasets for clients across academia and industry.

• Proven Expertise: Extensive track record in performing complex HiChIP experiments from diverse cell types.
• Data Quality Assurance: Each project is guided by stringent QC metrics to ensure reliable, publication-ready results.
• End-to-End Support: From experimental design to advanced bioinformatics analysis, we provide full-service solutions tailored to your research goals.

At a glance

• Workflow Overview
• Key Applications of HiChIP
• Advantages of HiChIP
• Sequencing Specifications
• HiChIP Sample Requirements
• Demo Results
• Frequently Asked Questions

What Is HiChIP?

HiChIP is an advanced genomic technique used to map protein-directed DNA-DNA interactions within the 3D architecture of the nucleus. By integrating the in situ chromatin interaction capture strategy of Hi-C with the specificity of chromatin immunoprecipitation (ChIP), HiChIP enables researchers to map high-resolution chromatin contacts centered on specific DNA-binding proteins.

This hybrid approach delivers three major advantages:

• High sensitivity for detecting protein-mediated chromatin loops
• Greater resolution compared to traditional Hi-C
• Minimal input requirements—ideal for limited or precious cell samples

Unlike ChIA-PET, which enriches target-bound DNA before spatial interaction capture, HiChIP reverses the order. It starts with in situ chromatin crosslinking and ligation, followed by targeted enrichment of protein-associated complexes via ChIP. This workflow improves efficiency and reduces background noise.

How HiChIP Works

The HiChIP protocol integrates steps from both Hi-C and ChIP-seq, optimising them for protein-centric chromatin interaction studies:

In situ crosslinking: Cells are fixed to preserve chromatin structure.

Spatial interaction capture: Chromatin is fragmented and in situ linkage is performed to preserve interactions between adjacent genomic regions.

ChIP enrichment: An antibody targeting the protein of interest pulls down DNA-protein complexes.

DNA purification and sequencing: Crosslinks are reversed, and biotin-labeled ligation products are purified and sequenced to reveal genome-wide interaction maps.

Overview of the HiChIP experimental principle.

HiChIP is particularly valuable for studying how transcription factors, histone modifications, or chromatin remodelers influence gene regulation across topologically associated domains (TADs).

Why Use HiChIP?

Researchers exploring 3D genome organisation often run into limitations when relying on single-method approaches like Hi-C or ChIP-seq. That's where HiChIP comes in—a hybrid technique that answers both the "where" and the "how" of protein-DNA interactions.

The Gaps in Traditional Methods

• Hi-C can chart genome-wide chromatin loops, but it's like getting a city map without landmarks. You see the connections—but not who built them.
• ChIP-seq shows where specific proteins bind on DNA, but offers a flat, one-dimensional view. It lacks the spatial insight needed to understand how these sites interact across the genome.

The HiChIP Breakthrough

HiChIP merges the strengths of both methods into a single, protein-targeted chromatin interaction tool.It pinpoints where a protein binds (like ChIP-seq).

It also maps which distant genomic regions physically connect at those sites (like Hi-C).

This dual capacity makes HiChIP especially powerful for:

• Investigating enhancer-promoter loops
• Understanding chromatin architecture, such as DNA loops and domains
• Uncovering the spatial gene regulation behind complex diseases

For teams focused on functional genomics or disease pathway analysis, HiChIP is a game-changer—offering clarity where older methods fall short.

Comparison of ChIA-PET and HiChIP Technologies

Workflow Overview

HiChIP follows a streamlined, in situ protocol to capture protein-directed chromatin interactions:

Crosslinking

Cells or tissues (animal or plant) are treated with formaldehyde to stabilise chromatin structures.

Chromatin Fragmentation & Spatial Interaction Linking

The genome is enzymatically fragmented, and spatially adjacent DNA fragments are ligated.

Immunoprecipitation (ChIP)

Antibodies are used to enrich for DNA fragments interacting with the target protein.

Library Construction & Sequencing

Chimeric DNA fragments are purified, indexed, and sequenced to identify genome-wide interaction patterns.

Simplified workflow of HiChIP sequencing service

Key Applications of HiChIP

Chromatin Interaction Profiling for Specific Proteins

HiChIP enables detailed mapping of where a protein binds and what distal regions it interacts with—ideal for studying chromatin architecture around specific regulators.

Mechanistic Studies of Transcription Factors

By identifying transcription factor binding sites across the genome, HiChIP helps clarify how these proteins control gene expression networks.

Epigenetic Regulation Analysis

HiChIP can uncover how histone modifications (e.g. methylation, acetylation) influence gene activity through long-range DNA contacts.

Dynamic Chromatin Architecture Studies

The method captures changes in chromatin folding across time or conditions, providing insight into dynamic 3D genome reorganisation.

HiChIP is increasingly used in functional genomics to understand how spatial genome organisation underpins gene regulation and cell identity.

Advantages of HiChIP

1. Exceptional Sensitivity with Low Input Requirements

Traditional Hi-C typically requires millions of cells to generate high-resolution contact maps. HiChIP overcomes this barrier with antibody-based enrichment, reducing input needs to just 100,000–500,000 cells.

Li et al. (2019) used only 50,000 human embryonic stem cells to map OCT4-driven regulatory networks in pluripotency.

2. Targeted and Efficient Data Output

Unlike Hi-C, which captures genome-wide interactions, HiChIP selectively retains only those contacts associated with the target protein. This reduces data volume by up to 90%, streamlining downstream analysis.

Sun et al. (2017) demonstrated how HiChIP pinpoints CTCF-bound boundaries of topologically associated domains (TADs), revealing its role as a "genome architect."

3. Dynamic Regulation Across Time or Condition

HiChIP is ideal for comparing chromatin interactions across developmental stages or disease states, offering fine time-resolution insights.

Zhang et al. (2022) showed that NF-κB rapidly remodels the 3D interaction landscape of inflammation-related genes during immune activation.

4. Multi-Omics Integration for Deeper Insights

HiChIP data can be integrated with ATAC-Seq and RNA-Seq to build a holistic view of how genome structure influences function and expression.

Cipta NO et al. (2025) used this approach to construct a comprehensive model linking chromatin structure, gene accessibility, and transcriptional output.

Sequencing Specifications

· Platform: Illumina NovaSeq 6000

· Read Mode: Paired-End 150 bp (PE150)

· Recommended Data Yield: 90–100 Gb per sample

HiChIP Sample Requirements

HiChIP Bioinformatics Analysis Overview

Demo Results

Summary of key HiChIP data analysis outputs.
Includes a loop distance distribution histogram, alignment and duplication statistics, FDR-based significant interaction count, and a loop MA plot highlighting differential chromatin interactions.

Visual summary of HiChIP differential interaction analysis.
Includes a volcano plot showing differentially enriched loops, a contact decay curve across genomic distances, and both box plot and violin plot visualizations of loop intensities between conditions.

Frequently Asked Questions

DNA Methylation Profiling (WGBS)

Bioinformatics & Multi-Omics Integration

Pore-C Service

Long Read Sequencing for Chromatin Conformation