SNAP-ChIP® Spike-In Controls

Nucleosome spike-ins for Quantitative ChIP-Seq

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Great Experiments Require Great Controls

Chromatin immunoprecipitation (ChIP) is a powerful and widely used approach to understanding chromatin regulation.

However, ChIP experiments have numerous sources of technical challenges:

  • Antibody cross-reactivity
  • Variation between replicates
  • Ill-defined normalization resources

Introducing SNAP-ChIP Spike-In Controls

Sample Normalization and Antibody Profiling for ChIP (SNAP-ChIP) Spike-In Controls provide a powerful new tool to generate highly reliable ChIP-seq data.

This technology uses a pool of recombinant nucleosomes carrying widely studied histone post-translational modifications (PTMs), each denoted by unique DNA barcodes.

SNAP-ChIP Spike-Ins are compatible with both native and cross-linked workflows. Simply spike-in the panel of interest prior to IP.

The nucleosomal DNA barcodes on the spike-ins can then be detected by qPCR or NGS and used to quantify antibody performance and normalize samples for reliable cross-experimental comparisons (Grzybowski et al. Nat Protoc 2019).

Essential Controls for Every ChIP Experiment


Ensure Antibody Specificity

Our findings and several publications have found that...
  • Histone peptide arrays used for antibody validation do not predict specificity in ChIP (Shah et al. Mol. Cell 2018).
  • Antibody specificity can vary significantly between production lots (see our blog).
  • The use of highly cited antibodies does not guarantee quality results (Shah et al. Mol. Cell 2018 and Lam et al. Nat. Comm. 2019).
  • Shah et al. and Lam et al. both found that many ChIP-grade antibodies cross-react, leading to incorrect biological interpretations (see figure).
Only by validating with SNAP-ChIP Spike-In Controls can scientists correctly identify and avoid cross-reactive antibodies which would confound their results.


Monitor Technical Variability

Our spike-in controls will make sure you never sequence another failed ChIP experiment again!

  • Seamlessly integrate into native and cross-linked ChIP workflows.
  • Serve as positive (on-target) and negative (off-target) controls.
  • Monitor technical variability in antibody specificity / efficiency across replicates.

qPCR of DNA barcodes provides a valuable STOP / GO step prior to expensive sequencing.


Normalize Between Experiments

SNAP-ChIP Spike-In Controls can also be used to normalize between experiments (Grzybowski et al. Mol Cell 2015, Shah et al. Mol. Cell 2018, and Lam et al. Nat. Comm. 2019).

  • Traditional methods for ChIP-seq normalization use exogenous chromatin spike-ins (e.g. Drosophila).
  • These approaches are problematic because they are heterogeneous, poorly defined, and inconsistent between lots.
  • SNAP-ChIP spike-ins provide a homogeneous defined control and are consistent from lot to lot.
EpiCypher is currently working to create more robust and streamlined SNAP-ChIP workflows for ChIP normalization.

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SNAP-ChIP® Spike-In Panels
EpiCypher SNAP-ChIP Panels are sold as a single tube which contains a mixture of DNA-barcoded recombinant nucleosomes with unique PTMs. Panel sets are focused around the most widely studied, disease-implicated histone PTMs. This enables flexibility in experimental design and allows users to characterize antibody specificity for their target of interest relative to the most likely cross-reactive species. SNAP-ChIP Panels are also available for studies of:
10 ChIP Rxns:                              $365
100 ChIP Rxns:                            $2,799
>100 Rxns & custom services:  **Contact for pricing**

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SNAP-ChIP® Certified Antibodies

Antibody selection is the single most important decision a researcher must make when designing a ChIP experiment, but rigorous antibody validation is costly and time-consuming. At EpiCypher, we recognize this challenge and have embarked on a massive effort to analyze and identify the highest performing ChIP antibodies.

SNAP-ChIP Certified Antibodies are best-in-class antibodies that have been rigorously validated using EpiCypher’s SNAP-ChIP spike-in technology. Custom antibody screening services available -- Contact us!

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About EpiCypher

A pioneer in the field of epigenetics and chromatin biology, EpiCypher is a biotechnology company developing transformative technologies to advance chromatin science and improve human health.

EpiCypher manufactures and sells a series of products and assay platforms that use recombinant “designer” nucleosomes (dNucs), including SNAP-ChIP® for quantitative ChIP applications, EpiDyne® for nucleosome remodeling assays, dCypher® to interrogate epigenetic regulators, recombinant histone binding proteins and enzymes, peptides and antibodies; and a broad range of custom substrate / assay development services.

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Questions? Give us a call.
(855) 374-2461