Integrated ATAC-MS Package
Single-enrichment, matched ATAC-seq + LC-MS/MS to link accessible loci with their regulators in one study.
ATAC-MS (Assay for Transposase-Accessible Chromatin combined with Mass Spectrometry) Service
Discover how chromatin accessibility and its protein regulators work together. Our ATAC-MS service provides dual-layer insights that transform complex biological questions into clear, testable hypotheses.
- Dual-Omics Integration — ATAC-seq + proteomics from the same chromatin fraction
- Low-Input Ready — reliable results from limited cells or tissues
- Quantitative Confidence — DIA/TMT with stringent QC metrics
- Regulatory Clarity — connect motifs, TFs, and histone PTMs to open loci
- Decision-Ready Data — harmonized outputs with visualization and interpretation
What Is ATAC-MS and How Does It Work?
ATAC-MS (Assay for Transposase-Accessible Chromatin combined with Mass Spectrometry) couples ATAC-seq with LC-MS/MS to connect where the genome is open with which chromatin-associated proteins and histone post-translational modifications (PTMs) regulate those regions.
- ATAC module: A hyperactive Tn5 transposase inserts sequencing adapters into accessible chromatin, generating libraries whose sequencing maps accessible sites, nucleosome positioning, and transcription factor (TF) footprints.
- MS module: The accessible-chromatin fraction (e.g., captured via biotin–streptavidin affinity workflows) is processed by LC-MS/MS to identify and quantify chromatin-bound proteins, histone variants, and their PTM states.
Outcome: A single, harmonized dataset linking where the genome is accessible to which regulators (proteins and PTMs) occupy or influence those loci—supporting testable hypotheses on transcriptional control, cell-state transitions, and mechanism-of-action profiling.
Typical Scientific Questions ATAC-MS Can Answer
- Which promoters, enhancers, and distal regulatory elements become more or less accessible under a given perturbation?
- What transcription factor (TF) motifs are enriched in newly accessible sites, and are the cognate TFs detected and regulated at the protein level?
- Which chromatin remodelers, histone modifiers, or cofactors co-vary with accessibility changes?
- Can we prioritize driver regulators that connect epigenomic shifts to pathway activation or repression?
- How do histone PTM profiles (e.g., acetylation, methylation) correlate with ATAC changes across conditions, lineages, or time points?
- What drug mechanism-of-action signatures emerge when integrating accessibility maps and the accessible-chromatin proteome?
Advantages of Our ATAC-MS Service
Same-Enrichment Dual-Omics — One Sample, Matched Layers
Matched ATAC-seq + LC-MS/MS from the accessible-chromatin fraction to minimize cross-sample variance.
Low-Input Compatibility
ATAC from ~1×10⁴–5×10⁴ cells; chromatin-proteomics from ~1×10⁵ nuclei (matrix-dependent).
Quantitative Rigor
DIA median CV ≤ 15%; TMT 16–18-plex cross-channel CV ≤ 10%; PSM/protein FDR ≤ 1%.
Depth on Regulatory Chromatin
Identify ~800–2,500 chromatin-associated proteins and quantify ~50–150 histone PTM sites per study.
Confident PTM Site Calls
Site localization probability ≥ 0.75 (Class I); mass accuracy ≤ 3 ppm; resolving power ≥ 60,000 (FWHM, m/z 200).
Reproducibility & Batch Robustness
ATAC inter-replicate Pearson r ≥ 0.90; proteomics RT alignment r ≥ 0.98; reference-channel normalization included.
Motif → Regulator Closure
Motif/footprint results (q ≤ 0.05) cross-validated against detected TFs/cofactors, yielding ~10–50 prioritized regulators per contrast.
Technical Services
Service Scope
Workflow and Instrumentation
Application
Sample Requirement
Deliverables
FAQ
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Scope of ATAC-MS Services at Creative Proteomics
ATAC-seq Package
Transposition → library prep → sequencing → analysis (alignment, peak calling, differential accessibility, TF footprinting, motif enrichment).
Accessible-Chromatin Proteomics Package
Affinity capture of accessible chromatin → LC-MS/MS identification/quantification of chromatin-associated proteins; optional histone variant/PTM panels.
Histone PTM & Proteoform Deep-Dive (Add-on)
Site-resolved PTM stoichiometry, combinatorial patterns, and variant profiling on chromatin.
Targeted Verification (Add-on)
PRM/SRM assays for selected proteins/PTMs; optional TMT reference-channel benchmarking.
Integrative Analytics & Multi-omics Reporting
Motif-to-TF linking, enhancer–gene assignment, pathway/network analysis; optional integration with client RNA-seq/phosphoproteomics.
Our ATAC-MS Service Workflow
1
Study Design Alignment
Clarify biological questions, contrasts, replicates, and quantification strategy (DIA/LFQ/isobaric). Define decision criteria for success.
2
Sample Receipt & Pre-Analytical QC
Assess integrity and matrix suitability; verify cell counts, nuclei quality, and buffer compatibility. Recommend native or mild crosslinking protocols based on goals.
3
Nuclei Preparation & Transposition
Optimize nuclei isolation; perform Tn5 transposition to tag accessible chromatin; monitor fragment profiles and insert-size periodicity.
4
Accessible Chromatin Enrichment & Fractionation
Affinity capture of transposed chromatin; split to DNA and protein fractions to enable parallel ATAC library prep and proteomics.
5
ATAC Library Construction & Sequencing
Library QC, size selection, and sequencing; deliver raw and processed alignment/peak files.
6
Proteomics Sample Processing & LC-MS/MS
Protein extraction, reduction/alkylation, tryptic digestion; optional fractionation; LC-MS/MS acquisition with the selected quant method.
7
Bioinformatics & Biostatistics
ATAC: alignment, peak calling, differential accessibility, footprinting, motif discovery.
Proteomics: identification, protein inference, quantification, PTM annotation, differential analysis.
Integration: motif-TF linking, promoter/enhancer assignment, pathway/connectivity analysis.
8
Reporting & Consultation
Structured results packages, QC dashboards, and figure-ready plots; review call to interpret findings and recommend follow-ups.
ATAC-MS Instrumentation & Technical Capabilities
Chromatin Accessibility (ATAC-seq) Module
Illumina NovaSeq 6000 / NextSeq 2000
- Paired-end sequencing, 50–150 bp reads
- Throughput: up to 3 Tb per run (NovaSeq S4 flow cell)
- Q30 score: ≥ 85–90% of bases
Illumina NovaSeq 6000
Typical QC metrics:
- TSS enrichment ≥ 6–8
- FRiP ≥ 0.20
- Clear mono-/di-/tri-nucleosome periodicity (~200 bp spacing)
Illumina NextSeq 2000
Mass Spectrometry (MS) Module
Orbitrap Exploris 480 / Orbitrap Fusion Lumos Tribrid (Thermo Scientific)
- Resolving power: up to 480,000 @ m/z 200 (Fusion Lumos); 60,000–240,000 @ m/z 200 (Exploris 480)
- Mass accuracy: ≤ 3 ppm (internal calibration)
- Dynamic range: > 5 orders of magnitude
- Scan speed: up to 20 Hz for data-dependent acquisition
Thermo Scientific Orbitrap Exploris 480
Q Exactive HF-X Orbitrap (Thermo Scientific)
- Resolving power: 120,000 @ m/z 200
- Maximum injection rate: 500 Hz (ultra-fast duty cycle)
- Sensitivity: detect low-femtomole peptide levels
Thermo Scientific Orbitrap Fusion Lumos Tribrid
LC Front-End: EASY-nLC 1200 nano-flow UHPLC
- Flow rate: 200–500 nL/min
- Columns: 75 µm × 25–50 cm, sub-2 µm C18 beads for high-resolution peptide separation
Thermo Scientific Q Exactive HF-X Orbitrap
Quantification Options
- DIA (Data-Independent Acquisition): Median CV ≤ 15% across replicates
- TMTpro 16–18 plex multiplexing: Cross-channel CV ≤ 10%
- LFQ (Label-Free Quantification): Alignment precision with RT correlation r ≥ 0.98
PTM and Histone Proteoform Profiling
- Targeted methods for histone-tail modifications
- Site localization probability ≥ 0.75 (Class I calls)
- Coverage of ~50–150 histone PTM sites per study
Application Scenarios
Epigenetic Regulation Studies
Map open chromatin regions and identify associated proteins to understand how regulatory complexes and histone modifications shape transcriptional programs.
Stem Cell & Developmental Biology
Track dynamic chromatin remodeling and proteomic shifts during lineage commitment, differentiation, and reprogramming.
Cancer & Disease Mechanism Research
Detect altered accessibility signatures and chromatin-bound factors that drive tumor progression, metabolic rewiring, or stress adaptation.
Drug Mechanism-of-Action Profiling
Assess how small molecules, biologics, or inhibitors remodel chromatin structure and modify chromatin-bound protein networks.
Comparative Cell-Type & Tissue Analysis
Distinguish subtypes, developmental stages, or treatment conditions by enhancer accessibility, transcription factor footprints, and associated proteomes.
Toxicology & Stress Response Research
Uncover early regulatory events and protein modifications triggered by chemical, metabolic, or environmental stressors.
Sample Requirements for ATAC-MS Assay
| Category | Requirements / Guidelines |
| Accepted Sample Types | Cell lines (adherent or suspension); Primary cells (PBMCs; immune subsets; ESCs/iPSCs/MSCs); Tissues (fresh or snap frozen, 10–50 mg typical); Organoids / spheroids (pellets preferred); Cryopreserved nuclei suspensions; FACS-sorted cells or nuclei (purity metadata recommended) |
| Input Amount | ATAC-seq: ~1×10⁴–5×10⁴ cells; Proteomics: ~1×10⁵–1×10⁶ nuclei (matrix dependent) |
| Preservation | Fresh or snap-frozen; store at –80 °C; avoid repeated freeze–thaw cycles |
| Exclusions | FFPE tissues, heavily crosslinked or degraded samples |
| Quality Control | Nuclei integrity ≥80%; cell viability >85% before nuclei prep |
| Buffer Guidelines | Avoid detergents (SDS, Triton), polymers, and high salt (>250 mM) |
| Replicates | ≥3 biological replicates recommended; technical replicates optional |
| Shipping | Snap-freeze pellets in liquid nitrogen; store at -80 °C; ship on dry ice with clear labels and metadata |
Deliverables: What You Get from Our ATAC-MS Service
- ATAC-seq data package — FASTQ, aligned BAM/BAI, BED peak sets, bigWig coverage tracks.
- Chromatin-proteomics package — RAW/mzML and search outputs; protein/peptide quant tables (DIA/LFQ/TMT); PTM/histone reports.
- Integrated insights — motif–TF–locus linking, promoter/enhancer mapping, prioritized regulators and pathway readouts.
- Visualization bundle — figure-ready plots (PNG/SVG), IGV session files, UCSC-compatible tracks.
- QC & methods — consolidated QC dashboard (e.g., TSS enrichment, FRiP, CVs, FDR) plus full methods, parameters, and data dictionary.
TSS enrichment curve showing strong signal enrichment around transcription start sites; QC value ~7.5, indicating high-quality ATAC-seq data.
Fragment length distribution with clear peaks for nucleosome-free region (NFR) and mono-, di-, tri-nucleosomes (~200, 400, 600 bp), confirming reliable library quality.
Representative promoter region showing higher accessibility in the treatment group, log2FC ≈ +1.2, q = 0.01, with AP-1 motif enrichment detected.
Scatter plot of protein abundances between control and treatment replicates; Pearson r ≈ 0.93, demonstrating high reproducibility.
Distribution of protein quantification CVs for DIA and TMT; DIA median CV ~12% and TMT cross-channel CV ~8%, within reliable ranges.
Chromatin-associated proteome coverage across strategies; ~1,500 proteins identified under standard conditions, exceeding 2,500 with deep profiling.
ATAC-MS vs ATAC-seq vs ChIP-seq vs Proteomics: Which Should You Choose?
| Aspect | ATAC-MS | ATAC-seq | ChIP-seq | DNase-seq / MNase-seq | Proteomics-only (Chromatin fraction) |
| Primary question answered | Which regions are open and which proteins/PTMs regulate them (same enrichment) | Where is chromatin open? | Where does a specific TF or histone mark bind? | Global accessibility or nucleosome organization | Which chromatin-associated proteins and histone PTMs are present/regulated? |
| Locus resolution & element coverage | Locus-level peaks linked to regulators measured on the same chromatin fraction | Peaks at promoters/enhancers; nucleosome phasing | Peak calls at TF/mark sites | Accessibility/nucleosome maps; limited enhancer annotation | No locus context |
| Direct regulator evidence | Motif/footprinting plus direct protein/PTM evidence (closure) | Motif/footprinting (inferred TFs) | Direct TF/mark evidence (antibody-specific) | None (no protein layer) | Direct protein IDs; PTM states |
| Protein/PTM quantification | Same as proteomics-only; chromatin-enriched; histone PTM panels (~50–150 sites) | — | — | — | DIA/LFQ/TMT; typical CV targets: DIA ≤15%, TMT ≤10% |
| Depth & coverage (typical ranges) | ~800–2,500 proteins with matched accessibility map | Genome-wide accessibility | Single factor/mark per assay | Genome-wide accessibility/nucleosomes | ~800–2,500 chromatin-associated proteins (matrix-dependent) |
| Input & matrix tolerance | Joint design; low-input options; same-sample split to DNA/protein | Works with low input; cells/tissues | Depends on antibody & abundance; often higher input | Often higher input; more complex | Nuclei/chromatin input typically higher than ATAC |
| QC anchors & stats | Combined: ATAC QC and proteomics QC (FDR ≤1%, CV targets) | TSS enrichment ≥6–8; FRiP ≥0.20; insert-size periodicity | Antibody validation; IDR reproducibility; peak quality metrics | Assay-specific cut sites/fragment patterns | PSM/protein FDR ≤1%; replicate CVs; mass accuracy |
| Integration potential | Native multi-omics: motif→TF/protein→pathway with locus context | Pairs well with RNA-seq | Validates specific regulators | Historical/orthogonal accessibility | Pairs with phospho- or total proteome |
| Best for | Mechanistic studies linking open loci to the regulators and pathways driving phenotype | Mapping open chromatin landscapes | Targeted validation of known TFs/marks | Nucleosome or legacy accessibility studies | Nuclear proteome composition & PTM dynamics |
You May Want to Know
What unique insights does ATAC-MS provide compared to single-omic methods?
ATAC-MS links chromatin accessibility with the chromatin-bound proteome in the same sample, delivering both where the genome is open and which proteins or histone PTMs regulate those regions.
Is ATAC-MS suitable for limited or precious samples?
Yes. Optimized low-input protocols allow analysis from as few as tens of thousands of cells or small frozen tissue pieces, making the method feasible for scarce clinical or developmental material.
How does ATAC-MS support regulator discovery?
Motif enrichment and footprinting from ATAC-seq are cross-validated with mass spectrometry data to directly confirm transcription factors, cofactors, or chromatin remodelers driving accessibility changes.
Can ATAC-MS capture dynamic changes across conditions?
Yes. By comparing accessibility and proteomic profiles across experimental contrasts, ATAC-MS highlights regulators and histone PTMs that shift during lineage differentiation, perturbation, or treatment.
Does ATAC-MS replace ChIP-seq?
Not entirely. ChIP-seq remains the best choice for validating a specific factor with a high-quality antibody. ATAC-MS is more powerful for unbiased, system-level discovery of regulators.
What types of research projects benefit most from ATAC-MS?
Studies in epigenetics, stem cell differentiation, cancer progression, and drug mechanism-of-action benefit most, as ATAC-MS can reveal how chromatin state and regulatory proteins change together.