HiChIP Sequencing Service

Genome conformation is central to gene regulation, but conventional genome-wide contact profiling can require deep sequencing because it captures all proximity ligations indiscriminately. HiChIP is a protein-centric chromatin conformation method that enriches long-range interactions associated with a factor of interest, improving data efficiency and interpretability. HiChIP was developed to boost sensitivity relative to ChIA-PET by improving the yield of conformation-informative reads by >10-fold and reducing input requirements by >100-fold, while also achieving greater signal-to-background than in situ Hi-C in factor-enriched contexts.

CD BioSciences' HiChIP sequencing service provides an end-to-end workflow—from experimental design and HiChIP library construction to sequencing and bioinformatic analysis—enabling efficient discovery and comparison of protein-anchored chromatin loops and interaction networks.

Introduction to HiChIP Sequencing

HiChIP integrates principles from in situ Hi-C and ChIP enrichment, coupled with transposase-mediated on-bead library construction. In HiChIP, long-range DNA contacts are established in situ within nuclei prior to lysis, which helps minimize false-positive interactions and improves contact capture efficiency. ChIP is then performed on the contact library to directly enrich interactions associated with the protein of interest, followed by paired-end sequencing to read out interacting genomic fragments.

Fig.1 HiChIP, a method that leverages principles of in situ Hi-C and transposase-mediated on-bead library construction. (Mumbach, M. R., et al., 2016)

Features of HiChIP Sequencing

1. High efficiency: improves conformation-informative read yield by >10-fold vs ChIA-PET.
2. Low input requirement: reported >100-fold lower input vs ChIA-PET.
3. Strong signal-to-background: HiChIP of cohesin shows greater signal-to-background than in situ Hi-C, with enrichment at loop anchors. 
4. Fast turnaround: protocol can be completed in as few as two days.
5. High proportion of informative PETs: >40% informative PETs reported in Smc1a HiChIP datasets.

Our Services

CD BioSciences provides a complete HiChIP sequencing service to map protein-anchored chromatin interactions efficiently and reproducibly. The workflow below represents the full service scope and typical execution steps for a HiChIP project, from wet-lab library construction through dry-lab analysis.

Study Design & Target Strategy

1. Define factor of interest (e.g., cohesin/CTCF-associated architecture, enhancer-associated marks, Pol II–linked regulatory programs)
2. Experimental design planning (controls, biological replicates, comparisons, expected interaction scale)
3. Antibody readiness review (ChIP-grade requirement; feasibility and risk assessment)

In Situ Contact Generation

1. Crosslinking and nuclei preparation
2. In situ digestion and end-fill/biotin marking, followed by proximity ligation to build contact libraries (Hi-C principles)

Chromatin Fragmentation & ChIP Enrichment

1. Chromatin shearing to ChIP-compatible fragment sizes
2. ChIP performed on the contact library to enrich interactions associated with the protein of interest

Post-ChIP DNA Recovery & Biotin Capture

1. Reverse crosslinking, purification, and quantification
2. Streptavidin-based biotin capture of ligation junction–containing DNA (contact-informative molecules)

On-Bead Tagmentation, PCR & Library QC

1. Transposase-mediated on-bead library construction (tagmentation)
2. PCR amplification and size selection; library complexity and size distribution QC
3. Paired-end sequencing strategy aligned with study scale and desired resolution

Bioinformatics Processing & Interaction/Loop Analysis

1. Read processing into unique informative PETs (method efficiency reporting can include PET fraction)
2. Contact matrix generation/normalization and loop calling (project-dependent)
3. Optional integration with factor occupancy context (e.g., peak overlap or enrichment reporting)

Supported Sample Types

1. Cultured Cells
2. Primary Cells
3. Fresh-Frozen Tissues and Solid Tumors

1. Cell Differentiation or Induction Models
2. Time-Course or Drug-Treated Samples
3. Other Types (Please Inquire)

Our Advantages

1. Protein-Directed 3D Genome Readout: HiChIP directly enriches interactions associated with your factor of interest, providing a targeted view of regulatory architecture.
2. High Efficiency and Low Input Potential: Reported >10-fold improvement in conformation-informative reads and >100-fold lower input requirement vs ChIA-PET in the original method description.
3. Strong Informative PET Fraction: 40% informative PETs reported for Smc1a HiChIP in GM and mES cell lines, supporting cost-effective sequencing depth planning.
4. Rapid, Reproducible Workflow: Described as robust and reproducible, and completable in as few as two days.

Build protein-anchored 3D interaction maps to reveal enhancer–promoter connectivity, architectural protein loops, and condition-driven chromatin rewiring. Contact us with your target factor, sample type, and study design—our team will recommend an optimized HiChIP strategy and deliver sequencing-ready data plus interpretation-focused outputs.

Reference

1. Mumbach, M. R., et al. (2016). HiChIP: efficient and sensitive analysis of protein-directed genome architecture. Nature methods, 13(11), 919–922.