Targeted Enhancer–Promoter Mapping
HiChIP projects that map enhancer–promoter contacts for your key genes and deliver loop maps and target lists.
HiChIP Sequencing Service for Targeted 3D Chromatin Mapping
Advancing your 3D genome research starts with choosing a method that delivers clarity, confidence and actionable insights. Our HiChIP sequencing service gives you protein-anchored, high-resolution chromatin interaction maps that reveal how regulatory factors connect enhancers, promoters and genes in three-dimensional space. Whether you're mapping transcription-factor mechanisms, interpreting non-coding variants or comparing treatment responses, we provide the end-to-end support needed to turn complex 3D data into clear biological answers.
- Targeted 3D insights — Map enhancer–promoter wiring anchored to your protein or histone mark.
- Designed for complex questions — Ideal for mechanism studies, drug response, and variant-to-gene links.
- Clear, publish-ready outputs — Loops, annotations and visualizations optimized for decision-making.
- Expert support — Recommendations on assay choice, antibodies and multi-omics integration.
What Is HiChIP?
HiChIP (in situ Hi-C followed by chromatin immunoprecipitation) is a targeted 3D genome mapping technology that captures chromatin contacts anchored by a specific protein or histone modification. By combining in-nucleus ligation, antibody-based enrichment, and transposase-driven library construction, HiChIP profiles long-range DNA interactions directly linked to defined regulatory factors. This makes it a powerful approach for connecting transcription factors or epigenetic marks to enhancer–promoter communication and higher-order chromatin architecture in cells.
Typical Scientific Questions HiChIP Can Answer
- Which enhancers physically interact with my gene of interest in a given cell type or condition?
- How does a specific transcription factor or co-factor organize local chromatin loops, and which genes fall within those loops?
- How are active or repressive histone modifications connected to promoter contacts, super-enhancers, or insulated regulatory domains?
- How does a small-molecule treatment, genetic perturbation, or environmental stimulus reshape 3D chromatin interactions around key pathways or biomarkers?
- Which distal genes are linked in three-dimensional space to GWAS loci or non-coding variants associated with disease traits?
- How do boundary and structural proteins such as CTCF or cohesin contribute to loop anchors and domain-like structures in my model system?
- Which regulatory contacts are gained or lost between different disease stages, cell states, or treatment conditions?
Why Choose Our HiChIP Sequencing Service
Protein-Centric 3D Enrichment — Delivers around tenfold more target-anchored contacts per read than legacy ChIA-style assays
Lower Sample Input — Uses up to about hundredfold less starting material than many classic interaction methods
Efficient Read Utilization — Directs more reads to factor-anchored loops instead of genome-wide background
End-to-End Project Support — Aligns study design, antibody choice, sequencing, and analysis to your key questions
Transparent QC Framework — Summarizes library, interaction, and enrichment metrics for fast go/no-go decisions
Loop-Focused Visualization — Provides contact maps and loop views ready for internal review and figure drafting
Multi-Omics Compatibility — Outputs are structured for seamless integration with RNA-seq, ATAC-seq, and ChIP-seq data
Technical Services
Service Scope
Method Comparison
Workflow
Platform
Sample Requirements
Deliverables
FAQ
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ChIRP-seq Mapping Solutions: What We Offer at Creative Proteomics
Transcription Factor–Centric HiChIP Projects
Factor-focused designs around your transcription factor or co-factor to reveal 3D loops and downstream target genes.
Drug and Perturbation Response HiChIP
Before–after HiChIP comparisons to show how treatments or genetic edits rewire chromatin interactions around critical pathways.
Disease Genetics and Non-Coding Variant HiChIP
Integration of HiChIP with GWAS or other non-coding variants to nominate likely target genes and mechanisms.
Comparative Loop Mapping Across Conditions
Multi-condition HiChIP studies that highlight loops and contacts gained, lost, or shifted between states or groups.
Structural Protein and Domain Organization HiChIP
Projects centered on CTCF, cohesin, or related factors to define loop anchors and domain-like 3D organization in your model.
Comparing 3D Chromatin Interaction Technologies
| Dimension | Hi-C | ChIA-PET | HiChIP | Capture-C / 4C (and related) |
| Primary focus | Global 3D genome architecture | Protein-anchored long-range interactions | Protein- or histone-mark–anchored 3D interactions with improved efficiency | Targeted interactions for one or a small set of viewpoints |
| Protein / mark specificity | None (unbiased) | High | High | Optional (depends on design; often promoter-centric) |
| Genome coverage | Whole genome | Subset of genome bound by the protein | Subset of genome bound by the protein or mark | Very focused regions around probe targets |
| Typical scientific question | "What is the overall chromatin organization in this cell type?" | "Which long-range contacts involve my protein of interest?" | "How does my protein or histone mark organize local regulatory loops and targets?" | "What contacts does this specific locus or gene have in 3D?" |
| Cell input requirement | Moderate to high | Often high, especially for rare factors | Lower than many legacy ChIA-PET–style protocols | Often moderate; depends on capture design and platform |
| Sequencing demand | High for loop-level resolution | High, to overcome sparse signal | Moderate to high, but more reads go to relevant contacts | Relatively moderate; focuses reads near targeted regions |
| Signal-to-noise for protein-centric loops | Lower; loops for a specific factor can be hard to isolate | Variable; can be noisy or fragmented | Typically higher signal-to-noise around target-anchored interactions | High around the captured viewpoints, but limited to those sites |
| Best suited for | Compartments, TADs, broad architectural changes between conditions | Protein-specific long-range contacts when sample is abundant | Enhancer–promoter wiring, factor- or mark-centric loops, GWAS-to-gene linking, perturbation studies with limited material | Detailed interaction profile of one or a few key genes, promoters, or loci |
| Not ideal when… | You only care about one factor or pathway and have limited budget | Sample amount is limited, or robust loops are needed across many conditions | You require fully unbiased whole-genome contact maps without focusing on any protein | You need genome-wide coverage or want to discover unexpected anchors far from pre-defined viewpoints |
Quick guidance:
- Choose Hi-C when your priority is global 3D architecture (compartments, TADs, overall folding).
- Choose ChIA-PET mainly in legacy or very specific contexts with ample material and a single protein of interest.
- Choose HiChIP when you want protein- or histone-mark–centric loops, often with limited input and higher usable signal per read.
- Choose Capture-C / 4C-type assays when you already know one or a few key loci and only need to map their specific interaction profiles.
Comparing HiChIP with 1D Epigenomic Profiling (ChIP-seq, ATAC-seq)
| Dimension | HiChIP | ChIP-seq | ATAC-seq |
| Primary readout | 3D chromatin interactions anchored by a protein or histone mark | 1D binding profile of a protein or histone modification along the genome | 1D chromatin accessibility (open regions) |
| 3D information | Yes, maps loops and contacts | No, linear occupancy only | No, accessibility only |
| Key question it answers | "Which regions contact each other in 3D around my factor, and which genes are connected?" | "Where does this protein or histone mark bind?" | "Which regions are open and potentially regulatory?" |
| Typical resolution | Loop- and domain-level, depending on depth | Peak-level along the linear genome | Peak-level open chromatin sites |
| Sample input | Moderate; lower than many classical interaction assays but higher than many 1D methods | Variable, often moderate | Generally low to moderate |
| Best suited for | Linking enhancers to target genes; mapping factor-anchored loops; interpreting non-coding variants in 3D | Defining target binding sites; motif analysis; selecting candidates for functional follow-up | Global mapping of active/open regulatory regions; discovering candidate enhancers and promoters |
| Main strengths | Directly connects regulatory elements, proteins/marks, and genes in 3D space | Widely used, mature pipelines; straightforward to interpret; compatible with many antibodies | Simple, robust measure of chromatin openness; good first pass for regulatory landscape |
| Main limitations | More complex experiment and analysis; needs more reads than pure 1D assays | No 3D context; cannot tell which enhancer contacts which gene | No binding specificity; does not tell which factor acts at each site or which gene is contacted |
| When HiChIP is preferred | When you need to know which enhancers contact which promoters for a given factor or mark, or how 3D regulation changes across conditions | When you need more than "where it binds" and want to understand how binding relates to 3D structure and gene targets | When you want to move from "open vs closed regions" to actual 3D connections between regulatory elements and genes |
When antibodies or in vivo ChIP are limiting, consider our DAP-Seq service.
For broader protein–DNA interaction profiling options, see our Protein–DNA Interaction Analysis platform.
For RNA-guided chromatin regulation, see our ChIRP-Seq service.
Step-by-Step Workflow for HiChIP Service
1
Crosslinking in intact cells to preserve native chromatin contacts.
2
Nuclei isolation and in situ Hi-C processing with restriction digestion, end repair, and biotin labeling of ligation junctions.
3
Nuclear lysis and chromatin fragmentation by sonication to generate suitable DNA fragment sizes.
4
ChIP enrichment using validated antibodies against the protein or histone mark of interest.
5
Reverse crosslinking and DNA purification to release interaction fragments.
6
Biotin pull-down and on-bead library preparation using a transposase-based strategy.
7
PCR amplification and sequencing on a high-throughput platform.
8
Quality control and bioinformatics analysis to call interactions, loops, and enriched regions.
HiChIP Instrumentation and Platform Capabilities
- Sequencing platform and mode
HiChIP projects run on Illumina NovaSeq with paired-end 150 bp (PE150) reads, supporting accurate mapping of chimeric ligation junctions and long-range contacts. - Library format
Dual-indexed HiChIP libraries compatible with pooled, multi-sample runs, enabling flexible study designs and cost-efficient sequencing. - Sequencing depth options
Data volume is tuned to your study goals—standard configurations for loop-level calling, with higher-depth options available when finer resolution or multi-condition comparisons are required. - Quality control
Each run includes library and interaction QC, so you receive clear metrics on data quality and suitability for downstream analysis.
NovaSeq 6000 (Fig from illumina)
HiChIP Sample Submission Guidelines
| Category | Recommended option | Details / notes |
| Sample type | Cultured cells or primary cells | Suspension or adherent cells from established lines or primary material suitable for crosslinking. |
| Cell state | Fresh viable cells or pre-fixed cell pellets | Viable cells for on-site fixation, or pellets fixed using a standard formaldehyde-based crosslinking protocol. |
| Minimum input per sample | ≥ 1–2 × 10⁷ cells (per condition) | Exact input depends on target abundance and antibody quality; lower input may be feasible after evaluation. |
| Supported species | Human, mouse, rat | Other species can be considered case by case, depending on antibody cross-reactivity and genome quality. |
| Fixation (if done on your side) | Mild crosslinking following ChIP-compatible protocols | Avoid over-fixation; use recommended buffer and timing. Detailed instructions available on request. |
| Shipping – fixed pellets | Crosslinked cell pellets on dry ice | Use clearly labeled screw-cap tubes, sealed bags, and sufficient dry ice for transit. |
| Shipping – live cells | Live cells in appropriate medium, cooled and shipped promptly | Use insulated packaging; avoid extreme temperature fluctuations and prolonged transit times. |
| Samples not recommended | Heavily contaminated or low-viability cultures | Strong microbial contamination, severe apoptosis, or heavy clumping can compromise ligation and ChIP enrichment. |
Deliverables: What You Get from Our HiChIP Service
- Raw sequencing data: Paired-end FASTQ files generated from HiChIP libraries.
- Processed alignment files: Cleaned, mapped BAM files and valid interaction pairs.
- Peak and interaction files: Target-enriched peaks, contact pairs, and loop calls in standard formats.
- Loop and regulatory annotations: Enhancer–promoter links, target gene tables, and region-level annotations.
- Quality control report: Library metrics, interaction QC, enrichment assessment, and replicate consistency.
- Optional full analysis package: Contact maps, virtual 4C, loop heatmaps, pathway summaries, and browser-ready tracks.
HiChIP contact map at a key locus with highlighted loops, plus ChIP-seq signal and gene track.
Genome browser view integrating HiChIP loops, HiChIP coverage, ChIP-seq, ATAC-seq and genes at one locus.
Volcano plot of differential HiChIP loops between Condition A and B (log₂ fold change vs −log₁₀ p-value).
Project-level HiChIP summary showing replicate correlation, loop distance profile, pathway enrichment and a representative locus.
You May Want to Know
When should I use HiChIP instead of Hi-C or ChIP-seq?
Use HiChIP when your core question is "which genes are connected in 3D by this protein or histone mark?".
Hi-C is better for global architecture questions; ChIP-seq and ATAC-seq are better when you only need 1D peak or accessibility maps.
If you send us a short project summary, we can recommend HiChIP or an alternative method based on your goal and material.
Is HiChIP suitable if I have limited cell numbers?
Often yes, especially compared with older ChIA-style methods. We review your target, expected cell yield, and species, then advise whether standard HiChIP, a lower-input variant, or a different assay is the safer choice. For borderline inputs, we may suggest starting with a pilot sample rather than a large full study.
Do I need existing ChIP-seq or ATAC-seq data before running HiChIP?
No, HiChIP can be run as a stand-alone assay. However, existing ChIP-seq or ATAC-seq data are very helpful for choosing targets, interpreting loops, and prioritizing genes, so we encourage you to share any prior datasets when planning the project.
What if I don't have a validated antibody for my target?
A good antibody is critical for HiChIP performance. If you already use an antibody successfully in ChIP-seq or CUT&Tag, we generally recommend that reagent. If not, we can suggest commonly used clones for standard targets and discuss feasibility tests or alternative marks (for example, an active histone mark instead of a difficult transcription factor).
Can you work with primary tissues or clinical samples, not just cell lines?
Yes, as long as the material can be converted into a high-quality, crosslinkable cell suspension. For primary cells and clinical material, we check viability, expected cell numbers, and isolation protocol before confirming a design. For solid tissue, we may recommend a small test batch or a staged project plan.
Do I need biological replicates for HiChIP?
For discovery and publication-level work, biological replicates are strongly recommended to support statistical analysis and QC. For early feasibility or method scouting, some clients begin with fewer samples and then expand once performance is confirmed. We can help you balance statistical power with sample and budget constraints.
How are HiChIP results analyzed and interpreted?
Standard projects include mapping, interaction calling and loop detection, with annotations that link loops to genes and regulatory features. You also receive figures such as contact maps, genome-browser views and differential-loop summaries that can be used directly in reports or manuscripts. If you plan deeper downstream modeling or integration with your in-house pipeline, we can align output formats accordingly.
Who owns the data, and how will I receive it?
You retain full ownership of all sequencing data and analysis results generated from your samples. Data are typically delivered via secure online transfer (FASTQ, processed files and reports), with the option to ship encrypted physical media if needed. We keep backup copies for a defined period for troubleshooting and re-analysis, unless you request deletion.
Can HiChIP be combined with other assays in the same project?
Yes. Many projects combine HiChIP with RNA-seq, ATAC-seq or standard ChIP-seq to connect 3D contacts, accessibility, binding and expression. We can design an integrated package so that sample handling, controls and analysis are coordinated across all assays.
