4-C/4C-Seq
4-C/4C-Seq
4C, also called 4C-seq, is a method similar to 3C and is sometimes called circular 3C. It allows the unbiased detection of all genomic regions that interact with a particular region of interest. In this method, DNA-protein complexes are crosslinked using formaldehyde. The sample is fragmented, and the DNA is ligated and digested. The resulting DNA fragments self-circularize, followed by reverse PCR and sequencing. Deep sequencing provides base-pair resolution of the ligated fragments.
Pros:
- Preferred strategy to assess the DNA contact profile of individual genomic sites
- Highly reproducible data
Cons:
- Will miss local interactions (< 50 kb) from the region of interest
- The large circles do not amplify efficiently
- 4C-Seq: Zhao Z., Tavoosidana G., Sjolinder M., Gondor A., Mariano P., et al. (2006) Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions. Nat Genet 38: 1341-1347
- 4C-Seq: Sajan S. A. and Hawkins R. D. Methods for identifying higher-order chromatin structure. Annu Rev Genomics Hum Genet. 2012;13:59-82
- Cai M., Kim S., Wang K., Farnham P. J., Coetzee G. A. and Lu W. 4C-seq revealed long-range interactions of a functional enhancer at the 8q24 prostate cancer risk locus. Sci Rep. 2016;6:22462
- Loviglio M. N., Leleu M., Mannik K., et al. Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes. Mol Psychiatry. 2016;
- Yang R., Kerschner J. L., Gosalia N., Neems D., Gorsic L. K., et al. Differential contribution of cis-regulatory elements to higher order chromatin structure and expression of the CFTR locus. Nucleic Acids Res. 2016;44:3082-3094
- Acemel R. D., Tena J. J., Irastorza-Azcarate I., Marletaz F., Gomez-Marin C., et al. A single three-dimensional chromatin compartment in amphioxus indicates a stepwise evolution of vertebrate Hox bimodal regulation. Nat Genet. 2016;48:336-341
- De S., Mitra A., Cheng Y., Pfeifer K. and Kassis J. A. Formation of a Polycomb-Domain in the Absence of Strong Polycomb Response Elements. PLoS Genet. 2016;12:e1006200
- Eckart N., Song Q., Yang R., et al. Functional Characterization of Schizophrenia-Associated Variation in CACNA1C. PLoS One. 2016;11:e0157086
- Kaaij L. J., Mokry M., Zhou M., Musheev M., Geeven G., et al. Enhancers reside in a unique epigenetic environment during early zebrafish development. Genome Biol. 2016;17:146
- Kandaswamy R., Sava G. P., Speedy H. E., et al. Genetic Predisposition to Chronic Lymphocytic Leukemia Is Mediated by a BMF Super-Enhancer Polymorphism. Cell Rep. 2016;16:2061-2067
- Lin C. Y., Erkek S., Tong Y., et al. Active medulloblastoma enhancers reveal subgroup-specific cellular origins. Nature. 2016;530:57-62
- Proudhon C., Snetkova V., Raviram R., Lobry C., Badri S., et al. Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation. Cell Rep. 2016;15:2159-2169
- Rocha P. P., Raviram R., Fu Y., Kim J., Luo V. M., et al. A Damage-Independent Role for 53BP1 that Impacts Break Order and Igh Architecture during Class Switch Recombination. Cell Rep. 2016;16:48-55
- Vermunt M. W., Tan S. C., Castelijns B., et al. Epigenomic annotation of gene regulatory alterations during evolution of the primate brain. Nat Neurosci. 2016;19:494-503
- Wang Q., Sawyer I. A., Sung M. H., et al. Cajal bodies are linked to genome conformation. Nat Commun. 2016;7:10966
- Wani A. H., Boettiger A. N., Schorderet P., et al. Chromatin topology is coupled to Polycomb group protein subnuclear organization. Nat Commun. 2016;7:10291