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Invitrogen™ MAGnify™ Chromatin Immunoprecipitation System

Catalog No. 492024
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24 reactions kit
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492024 24 reactions kit
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Catalog No. 492024 Supplier Invitrogen™ Supplier No. 492024
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Streamlined, optimized assay for the enrichment of chromatin/protein complexes and DNA recovery using magnetic bead capture technology.

The isolated DNA is ready for downstream analysis by methods such as PCR- or qPCR-based assays, or massive parallel DNA sequencing. Chromatin immunoprecipitation (ChIP) is a powerful technique for studying the association of certain proteins with specific regions of the genome. These sequence-specific DNA-binding proteins are believed to play a role in such cellular processes as DNA replication, recombination, repair, and segregation; chromosomal stability; cell-cycle progression; and epigenetic silencing. In a standard ChIP assay, a cell is fixed via formaldehyde treatment and the chromatin is sheared and immunoprecipitated via a highly specific antibody. The researcher then analyzes the DNA to identify the genomic regions where the chromatin-associated proteins bind to the chromatin in vivo. When using the MAGnify system, cells or tissue are treated with formaldehyde to generate protein-protein and protein-DNA crosslinks between molecules in close proximity within the chromatin complex. The cells are then lysed, and the chromatin is released from the nuclei and sheared by sonication to reduce the average DNA fragment size to 200 to 500 bp for analysis by quantitative real-time PCR (qPCR) or 100 to 300 bp for analysis by massive parallel DNA sequencing. You then immunoprecipitate and isolate the crosslinked protein of interest using a specific ChIP-qualified antibody conjugated to Dynabeads™ Protein A/G. The formaldehyde crosslinking is reversed by heat treatment, and the DNA associated with that protein is purified. The DNA is now ready for downstream analyses such as end-point PCR or quantitative PCR (qPCR), genome-wide analyses using promoter-tiling arrays, or next-generation sequencing. In PCR/qPCR analysis, primers are designed to span the desired DNA sequence of interest, and the data demonstrates whether the specific protein of interest is associated in vivo with that DNA region.

  • Sensitive: obtain results with lower sample amounts than required with traditional ChIP workflows
  • Rapid: protocol can be completed in a single day, compared with 2 to 3 days for traditional ChIP assay

Specifications

Content And Storage Module 1 (shipped on wet ice, store at 4°C):
• 2 × 1 ml Glycine (1.25 M)
• 250 μl Dynabeads™ Protein A/G (do not freeze)
• 1.4 ml Reverse Crosslinking Buffer
• 500 μl DNA Purification Magnetic Beads (do not freeze)
• 1.4 ml DNA Purification Buffer
• 200 μl Proteinase K (20 mg/ml)

Module 2 (shipped on wet ice, store at 4°C):
• 10 ml IP Buffer 1
• 7.5 ml IP Buffer 2
• 8 ml DNA Wash Buffer
• 7.2 ml DNA Elution Buffer

Module 3 (shipped on dry ice, store at -20°C):
• 100 μl Protease Inhibitors (200X)
• 15 μl Mouse IgG (1 μg/μl)
• 15 μl Rabbit IgG (1 μg/μl)

Module (shipped on dry ice, store at -20°C):
• 8 ml Dilution Buffer
• 3.6 ml Lysis Buffer
High-throughput Compatibility High-throughput Compatible
Sample Type Cell Cultures, DNA (Genomic), Live Cells
Product Line MAGnify
Quantity 24 reactions kit
For Use With (Application) Chromatin Immunoprecipitation
Type Immunoprecipitation/Co-Immunoprecipitation Kit
Sufficient For 24 Reactions
What is the recommended amount of starting material when working with the MAGnify Chromatin Immunoprecipitation System kit?

For each ChIP reaction, we recommend using 10,000-300,000 cells or 0.167-5 mg of tissue. To ensure consistency and decrease experimental variability, we recommend preparing a common chromatin batch suitable for multiple ChIP experiments. Note that following lysis, samples are at a concentration of 1 million cells/50 µL.

I am getting equivalent PCR signal from positive and negative control IP samples. Why is this?

There might be excess chromatin or antibody added to the IP, or insufficient amount of DNA template added into the PCR reaction. Also your PCR conditions might need optimizing. Try decreasing the number of amplification cycles in PCR. Finally, it is ideal to have duplicate or triplicate runs for each IP to identify any issues, like human or product errors.

I am not getting PCR signal in the experimental IP samples, while the results from positive and negative control IPs are as expected. What happened?

The most possible cause is the antibody does not function in IP. Not all antibodies used for western blotting will work well in ChIP. You need to verify the antibody is qualified for ChIP or IP applications. And try adding more antibody to the IP reaction and more DNA template to the PCR.

I am not getting any PCR signal with the positive control IP samples. Do you have some tips?

This is likely to be caused by insufficient chromatin amount in the IP reaction or insufficient antibody incubation time. We also recommend optimizing the crosslinking condition, and monitoring sonication of nuclei by microscope to ensure complete lysis.

I am doing chromatin analysis and am not getting PCR signal in the total input control samples. What should I do?

First make sure that the PCR condition is fully optimized and check the primer design. Then try increasing the amount of template DNA added to the PCR reaction. Finally, evaluate sonication of nuclei by microscope to ensure complete lysis.

What is the optimal fragment size for a ChIP reaction?

Shearing of the chromatin into appropriate fragments is required to ensure optimal ChIP results. Ideal shearing should yield DNA fragments between 200 and 1000 bp in length. ~200-500 bp fragments are usually used in downstream qPCR analysis and ~100-300 bp fragments are used in massive parallel DNA sequencing downstream analysis.

Does the MAGnify Chromatin Immunoprecipitation (ChIP) System work with FFPE samples?

Yes. Please refer to this paper for chromatin preparation protocol from FFPE samples: Fanelli M et al. Nature Protocol, 2011; 6:1905-1919. Our R&D has collaborated with the authors to confirm that the MAGnify Chromatin Immunoprecipitation (ChIP) System is compatible with this protocol.

For fixed but not embedded samples (e.g., 10 min in 1% PFA), the standard protocol will work. No further modification is needed.

Is the MAGnify Chromatin Immunoprecipitation (ChIP) System compatible with next-generation sequencing?

Yes. The MAGnify Chromatin Immunoprecipitation (ChIP) System has been validated for all major next-generation sequencing platforms. Usually 1-10 ng ChIP DNA is enough for next-generation sequencing. For next-generation sequencing support, please visit our Next-Generation Sequencing Support Center (thermofisher.com/ngssupport).

What controls should I use for ChIP?

We recommend the following controls:

- Negative control antibody: Either do not use a primary antibody, or use the normal rabbit IgG or mouse IgG isotype control.
- Positive control antibody: This control ensures that each step of the procedure is working. For example, we observe consistent enrichment of heterochromatin markers such as H3-K9Me3 at the satellite repeat locus (SAT-2).
- Negative control PCR primer: This control is designed against a sequence that would not be enriched by your chromatin IP procedure.
- Input DNA control: Input DNA is DNA obtained from chromatin that has not been immunoprecipitated and has been reversed crosslinked similar to your samples. It is a control for PCR effectiveness and utilized in ChIP sequencing data analysis.

Which method do you recommend to shear DNA fragments for ChIP?

Both sonication and enzyme digestion are widely used for ChIP. Micrococcal nuclease results in greater reproducibility and allows better control of the fragment sizes. However, it can take more optimization and the enzyme can be compromised and fail to work properly.

What is the expected yield in ChIP reactions?

Many factors influence yield, including cell type, target protein, antibody, etc. Generally speaking, anywhere between 0.5 ng to >10 ng can be obtained per ChIP reaction. Yields are usually too low to be measured using a NanoDrop spectrophotometer.

What is the recommended amount of starting material when working with your ChIP kits?

For each ChIP reaction, the MAGnify Chromatin Immunoprecipitation (ChIP) System recommends using 10,000-300,000 cells or 0.167 - 5 mg of tissue. The Thermo Scientific Agarose ChIP Kit and Thermo Scientific Magnetic ChIP Kit recommend 2 - 4 x 10E6 cells per ChIP reaction. To ensure consistency and decrease experimental variability, we recommend preparing a common chromatin batch suitable for multiple ChIP experiments.


For Research Use Only. Not for use in diagnostic procedures.