Micro-C Sequencing Service

Micro-C is a high-resolution chromosome conformation capture method derived from Hi-C. By introducing a micrococcal nuclease (MNase) digestion step, Micro-C measures contacts between pairs of crosslinked nucleosomes, enabling investigation of chromatin organization at ~100 bp (nucleosome-level) resolution. Side-by-side comparisons have shown that Micro-C can robustly recapitulate key 3D genome features such as TADs and chromatin loops with high reproducibility and comparable data quality, while revealing finer-scale structures below conventional Hi-C. CD BioSciences' Micro-C sequencing service provides an end-to-end solution—from experimental design and MNase optimization to sequencing-ready libraries and downstream 3D genome analysis—helping you resolve chromatin folding and regulatory interactions at nucleosome scale.

Introduction to Micro-C Sequencing

Micro-C captures spatial proximity of chromatin loci through crosslinking and proximity ligation, similar to Hi-C, but uses MNase digestion to fragment chromatin toward nucleosome-sized units. This enables detection of chromatin features at scales that are difficult to resolve with restriction enzyme–based Hi-C.

Micro-C data can be used to profile key architectural features including:

1. Topologically Associating Domains (TADs)—local domains with higher internal interaction frequency.
2. Chromatin loops—pairs of loci that are distant in linear genome distance but spatially proximal, often appearing as sharp "dots" on contact maps.

Fig.1 The heatmaps of the averaged contact maps of real Micro-C, Hi-C, C2c-predicted Micro-C, and HiCNN-enhanced HiC that centered at the loops from the real Micro-C data. (Zhu, H., et al., 2024)

Features of Micro-C Sequencing

1. Nucleosome-level contact mapping enabled by MNase digestion and nucleosome-pair contact measurement (up to ~100 bp resolution).
2. Enhanced detection of fine-scale chromatin folding below the scale of conventional TAD-level organization.
3. Robust recovery of canonical 3D genome features (TADs and loops) with strong reproducibility.
4. High technical rigor requirements, including tight MNase digestion control and deeper/high-resolution sequencing planning.

Our Services

CD BioSciences offers a complete Micro-C sequencing service designed for reliable nucleosome-resolution contact maps and interpretable 3D genome features. Given the technical sensitivity of Micro-C—especially MNase digestion and sequencing depth requirements—our workflow is built around standardized QC checkpoints to ensure reproducibility and data usability.

Study Design & Sample Intake

1. Define study goals (loop/TAD discovery, condition comparison, perturbation/time-course)
2. Recommend experimental design (controls, biological replicates, target resolution)
3. Sample review and feasibility assessment (cell/tissue type, input amount, expected chromatin state)

Micro-C Library Construction

1. Crosslinking to preserve chromatin contacts in vivo
2. MNase digestion and fragmentation tuning to achieve nucleosome-scale resolution
3. End repair, proximity ligation, and reverse crosslinking
4. DNA purification and sequencing-ready library preparation with QC checkpoints

Bioinformatics & 3D Genome Interpretation

1. Read alignment, filtering, and deduplication
2. Contact matrix generation and normalization at selected resolutions
3. Detection/annotation of 3D genome features (loops, domains/boundaries)
4. Comparative analysis across conditions (optional) and final report delivery

Sequencing & Library Quality Control

1. Library quantification and size distribution assessment
2. Paired-end sequencing strategy aligned with desired map resolution
3. Core QC readouts (library complexity, valid contact yield, duplication metrics)

Supported Sample Types

1. Cultured Cells
2. Primary Cells
3. Fresh-Frozen Tissues

1. Organoids and 3D Culture Models
2. Time-Course or Drug-Treated Samples
3. Other Types (Please Inquire)

Our Advantages

1. MNase Digestion Control Built-In: Micro-C performance depends on digestion precision; our workflow emphasizes optimization and QC to reduce batch variability.
2. Resolution-Driven Study Design: We plan sequencing and analysis to match your target feature scale—supporting fine-scale loop and domain discovery.
3. Actionable 3D Genome Interpretation: Deliverables focus on interpretable loops/TADs and condition-to-condition changes aligned with regulatory biology questions.

Resolve chromatin architecture at nucleosome scale with CD BioSciences' Micro-C sequencing service. Contact us with your sample type, organism, and study goals—we'll recommend an optimized Micro-C design and deliver high-resolution contact maps ready for downstream regulatory and mechanistic discovery.

Reference

1. Zhu, H., et al. (2024). C2c: Predicting Micro-C from Hi-C. Genes, 15(6), 673.