Actual Ligation Frequencies in the Chromosome Conformation Capture Procedure
Open accessAbstract
Chromosome conformation capture (3C) and derivative experimental procedures are used to estimate the spatial proximity between different genomic elements, thus providing information about the 3D organization of genomic domains and whole genomes within the nucleus. All C-methods are based on the proximity ligation-the preferential ligation of joined DNA fragments obtained upon restriction enzyme digestion of in vivo cross-linked chromatin. Here, using the mouse beta-globin genes in erythroid cells as a model, we estimated the actual frequencies of ligation between the fragments bearing the promoter of the major beta-globin gene and its distant enhancers and showed that the number of ligation products produced does not exceed 1% of all fragments subjected to the ligation. Although this low yield of 3C ligation products may be explained entirely by technical issues, it may as well reflect a low frequency of interaction between DNA regulatory elements in vivo.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Even the strongest C-captured contacts are detected in less than 10% of cells.
“This can explain why even the strongest C-captured contacts are detected in less than 10% of cells [107,108,109].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [108]
The Discussion reports that ligation frequencies for the studied beta-globin promoter–enhancer contacts were in the tenths of a percent, supporting a low detection yield. But the Introduction says 3C cannot estimate the proportion of cells in which two sequences interact, and the Abstract notes that the low yield could be entirely technical. The paper therefore does not establish the claim’s percentage of cells or its extension to the strongest contacts generally. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Capturing Chromosome Conformation
Dekker, J., Rippe, K., Dekker, M., & Kleckner, N. (2002) · Science · doi:10.1126/science.1067799 · Cited by 3,652 · see citing works
Looping and Interaction between Hypersensitive Sites in the Active β-globin Locus
Tolhuis, B., Palstra, R.-J., Splinter, E., Grosveld, F., & de Laat, W. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00781-5 · Cited by 1,344 · see citing works
A decade of 3C technologies: insights into nuclear organization.Preprint
de Wit, E., & de Laat, W. (2012) · Genes & Development · doi:10.1101/gad.179804.111 · Cited by 727 · see citing works
Quantitative analysis of chromosome conformation capture assays (3C-qPCR)
Hagège, H., Klous, P., Braem, C., Splinter, E., Dekker, J., Cathala, G., de Laat, W., & Forné, T. (2007) · Nature Protocols · doi:10.1038/nprot.2007.243 · Cited by 720 · cited 3× · see citing works
“As all biochemical protocols, the 3C cannot provide for estimating the proportion of cells in which two particular DNA sequences interact, and can only be used to analyzing the average interaction pattern for a given cell population [4,6].”
BackgroundMethodCTCF mediates long-range chromatin looping and local histone modification in the β-globin locus
Splinter, E., Heath, H., Kooren, J., Palstra, R.-J., Klous, P., Grosveld, F., Galjart, N., & de Laat, W. (2006) · Genes & Development · doi:10.1101/gad.399506 · Cited by 677 · see citing works
The β-globin nuclear compartment in development and erythroid differentiation
Palstra, R.-J., Tolhuis, B., Splinter, E., Nijmeijer, R., Grosveld, F., & de Laat, W. (2003) · Nature Genetics · doi:10.1038/ng1244 · Cited by 559 · see citing works
Transcription complex stability and chromatin dynamics in vivo
Wijgerde, M., Grosveld, F. G., & Fraser, P. (1995) · Nature · doi:10.1038/377209a0 · Cited by 471 · see citing works
Zhang, J., Socolovsky, M., Gross, A. W., & Lodish, H. F. (2003) · Blood · doi:10.1182/blood-2003-05-1479 · Cited by 386 · see citing works
The three 'C' s of chromosome conformation capture: controls, controls, controls
Dekker, J. (2005) · Nature Methods · doi:10.1038/nmeth823 · Cited by 347 · see citing works
Analysis of long-range chromatin interactions using Chromosome Conformation Capture
Naumova, N., Smith, E. M., Zhan, Y., & Dekker, J. (2012) · Methods · doi:10.1016/j.ymeth.2012.07.022 · Cited by 178 · see citing works
Mechanisms of developmental control of transcription in the murine α- and β-globin lociPreprint
Trimborn, T., Gribnau, J. H., Grosveld, F. G., & Fraser, P. (1999) · Genes & Development · doi:10.1101/gad.13.1.112 · Cited by 145 · see citing works
Comet, I. V., Schuettengruber, B., Sexton, T., & Cavalli, G. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002059108 · Cited by 124 · see citing works
3C Technology: Analyzing the Spatial Organization of Genomic Loci In Vivo
Splinter, E., Grosveld, F. G., & de Laat, W. L. (2003) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(03)75030-7 · Cited by 121 · see citing works
Chromatin interaction mechanism of transcriptional control in vivo
Gribnau, J. H., de Boer, E., Trimborn, T., Wijgerde, M., Milot, É., Grosveld, F. G., & Fraser, P. (1998) · The EMBO Journal · doi:10.1093/emboj/17.20.6020 · Cited by 94 · see citing works
Gavrilov, A. A., Gushchanskaya, E. S., Strelkova, O., Zhironkina, O., Kireev, I. I., Iarovaia, O. V., & Razin, S. V. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt067 · Cited by 87 · see citing works
Self-citationChapter 5 Three‐Dimensional Organization of Gene Expression in Erythroid Cells
de Laat, W. L., Klous, P., Kooren, J. A., Noordermeer, D., Palstra, R.-J. T. S., Simonis, M., Splinter, E., & Grosveld, F. G. (2008) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(07)00005-1 · Cited by 83 · see citing works
Chromosome conformation capture (from 3C to 5C) and its ChIP-based modification
Gavrilov, A., Eivazova, E., Pirozhkova, I., Lipinski, M., Razin, S., & Vassetzky, Y. (2009) · Methods in molecular biology · doi:10.1007/978-1-60327-414-2_12 · Cited by 82 · cited 1× · see citing works
“In a conventional 3C experiment, ligation frequencies are determined by qPCR with amplicons spanning ligation junctions of interest and expressed in units reflecting the relative amounts of the ligation products [4,5].”
MethodFrom cells to chromatin: Capturing snapshots of genome organization with 5C technology
Ferraiuolo, M. A., Sanyal, A., Naumova, N., Dekker, J., & Dostie, J. (2012) · Methods · doi:10.1016/j.ymeth.2012.10.011 · Cited by 50 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Enhancer Function in the 3D Genome
Razin, S. V., Ulianov, S. V., & Iarovaia, O. V. (2023) · Genes · doi:10.3390/genes14061277 · Cited by 15 · see citing works
Self-citation
- Authors
- Gavrilov, A. A., Golov, A. K., & Razin, S. V.
- Affiliations
- Russian Academy of Sciences (RU)
- Corresponding author
- Gavrilov, Alexey A.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-03-26
- Volume
- 8
- Issue
- 3
- Pages
- e60403
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3608588
- OpenAlex
- W2144731851
- Cited by
- 25
- References
- 18
- Citations by year
- 2025: 2 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 5 · 2015: 4 · 2014: 2 · 2013: 2
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Centre National de la Recherche Scientifique
- Russian Academy of Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- chromosome conformation capture, 3D genome organization, enhancer-promoter interactions, beta-globin gene, erythroid cells, DNA regulatory elements, in vivo cross-linking
- MeSH terms
- Animals, Chromosomes, DNA, DNA Restriction Enzymes, Enhancer Elements, Genetic, Nucleic Acid Conformation, Promoter Regions, Genetic, Genomics, Erythroid Cells, Mice, beta-Globins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
