The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression
Open accessAbstract
Chromatin topology is intricately linked to gene expression, yet its functional requirement remains unclear. Here, we comprehensively assessed the interplay between genome topology and gene expression using highly rearranged chromosomes (balancers) spanning ~75% of the Drosophila genome. Using transheterozyte (balancer/wild-type) embryos, we measured allele-specific changes in topology and gene expression in cis, while minimizing trans effects. Through genome sequencing, we resolved eight large nested inversions, smaller inversions, duplications and thousands of deletions. These extensive rearrangements caused many changes to chromatin topology, disrupting long-range loops, topologically associating domains (TADs) and promoter interactions, yet these are not predictive of changes in expression. Gene expression is generally not altered around inversion breakpoints, indicating that mis-appropriate enhancer-promoter activation is a rare event. Similarly, shuffling or fusing TADs, changing intra-TAD connections and disrupting long-range inter-TAD loops does not alter expression for the majority of genes. Our results suggest that properties other than chromatin topology ensure productive enhancer-promoter interactions.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the considerable TAD re-arrangements observed in Drosophila balancer chromosomes compared with their wild-type counterparts result in changes in the expression of only ~ 10% of genes [449].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [449]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Third, biochemical annotations fail to specify which gene(s) a putative enhancer regulates, let alone the degree of activation conferred78,79.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [78]
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.
Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Rao, S. S. P., Huntley, M. H., Durand, N. C., Stamenova, E. K., Bochkov, I. D., Robinson, J. T., Sanborn, A. L., Machol, I., Omer, A. D., Lander, E. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.021 · Cited by 9,212
Primer3—new capabilities and interfaces
Untergasser, A., Cutcutache, I., Kõressaar, T., Ye, J., Faircloth, B., Remm, M., & Rozen, S. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks596 · Cited by 9,165
Topological domains in mammalian genomes identified by analysis of chromatin interactions
Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J. S., & Ren, B. (2012) · Nature · doi:10.1038/nature11082 · Cited by 6,829
The Genome of Drosophila Melanogaster
Lindsley, D. L., & Zimm, G. G. (1992) · Cited by 3,098
Spatial partitioning of the regulatory landscape of the X-inactivation centre
Nora, E. P., Lajoie, B. R., Schulz, E. G., Giorgetti, L., Okamoto, I., Servant, N., Piolot, T., van Berkum, N. L., Meisig, J., Sedat, J., et al. (2012) · Nature · doi:10.1038/nature11049 · Cited by 2,895
DELLY: structural variant discovery by integrated paired-end and split-read analysis
Rausch, T., Zichner, T., Schlattl, A., Stütz, A. M., Beneš, V., & Korbel, J. O. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts378 · Cited by 2,438
Self-citationAn integrated map of structural variation in 2,504 human genomes
Sudmant, P. H., Rausch, T., Gardner, E. J., Handsaker, R. E., Abyzov, A., Huddleston, J., Zhang, Y., Ye, K., Jun, G., Hsi-Yang Fritz, M., et al. (2015) · Nature · doi:10.1038/nature15394 · Cited by 2,354
Self-citationTranscription factors: from enhancer binding to developmental control
Spitz, F., & Furlong, E. E. M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3207 · Cited by 2,227
Self-citationDisruptions of Topological Chromatin Domains Cause Pathogenic Rewiring of Gene-Enhancer Interactions
Lupiáñez, D. G., Kraft, K., Heinrich, V., Krawitz, P., Brancati, F., Klopocki, E., Horn, D., Kayserili, H., Opitz, J. M., Laxova, R., et al. (2015) · Cell · doi:10.1016/j.cell.2015.04.004 · Cited by 2,132
Three-dimensional folding and functional organization principles of the Drosophila genome
Sexton, T., Yaffe, E., Kenigsberg, E., Bantignies, F., Leblanc, B., Hoichman, M., Parrinello, H., Tanay, A., & Cavalli, G. (2012) · Cell · doi:10.1016/j.cell.2012.01.010 · Cited by 1,983
Cohesin Loss Eliminates All Loop Domains
Rao, S. S. P., Huang, S.-C., Glenn St Hilaire, B., Engreitz, J. M., Perez, E. M., Kieffer-Kwon, K.-R., Sanborn, A. L., Johnstone, S. E., Bascom, G. D., Bochkov, I. D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.026 · Cited by 1,883
Drosophila: A laboratory handbook
Ashburner, M. (1990) · Trends in Ecology & Evolution · doi:10.1016/0169-5347(90)90121-s · Cited by 1,751
Nora, E. P., Goloborodko, A., Valton, A.-L., Gibcus, J. H., Uebersohn, A., Abdennur, N., Dekker, J., Mirny, L. A., & Bruneau, B. G. (2017) · Cell · doi:10.1016/j.cell.2017.05.004 · Cited by 1,709
The Drosophila melanogaster Genetic Reference Panel
Mackay, T. F. C., Richards, S., Stone, E. A., Barbadilla, A., Ayroles, J. F., Zhu, D., Casillas, S., Han, Y., Magwire, M. M., Cridland, J. M., et al. (2012) · Nature · doi:10.1038/nature10811 · Cited by 1,654
Insulator dysfunction and oncogene activation in IDH mutant gliomas
Flavahan, W. A., Drier, Y., Liau, B. B., Gillespie, S. M., Venteicher, A. S., Stemmer-Rachamimov, A. O., Suvà, M. L., & Bernstein, B. E. (2016) · Nature · doi:10.1038/nature16490 · Cited by 1,288
A high-resolution map of the three-dimensional chromatin interactome in human cells
Jin, F., Li, Y., Dixon, J. R., Selvaraj, S., Ye, Z., Lee, A. Y., Yen, C.-A., Schmitt, A. D., Espinoza, C. A., & Ren, B. (2013) · Nature · doi:10.1038/nature12644 · Cited by 1,208
Two independent modes of chromatin organization revealed by cohesin removal
Schwarzer, W., Abdennur, N., Goloborodko, A., Pekowska, A., Fudenberg, G., Loe-Mie, Y., Fonseca, N. A., Huber, W., Haering, C. H., Mirny, L., et al. (2017) · Nature · doi:10.1038/nature24281 · Cited by 1,196
Paired-End Mapping Reveals Extensive Structural Variation in the Human Genome
Korbel, J. O., Urban, A. E., Affourtit, J. P., Godwin, B., Grubert, F., Simons, J. F., Kim, P. M., Palejev, D., Carriero, N. J., Du, L., et al. (2007) · Science · doi:10.1126/science.1149504 · Cited by 1,163
Self-citationThe whole-genome landscape of medulloblastoma subtypes
Northcott, P. A., Buchhalter, I., Morrissy, A. S., Hovestadt, V., Weischenfeldt, J., Ehrenberger, T., Gröbner, S., Segura-Wang, M., Zichner, T., Rudneva, V. A., et al. (2017) · Nature · doi:10.1038/nature22973 · Cited by 1,112
Self-citationActivation of proto-oncogenes by disruption of chromosome neighborhoods
Hnisz, D., Weintraub, A. S., Day, D. S., Valton, A.-L., Bak, R. O., Li, C. H., Goldmann, J., Lajoie, B. R., Fan, Z. P., Sigova, A. A., et al. (2016) · Science · doi:10.1126/science.aad9024 · Cited by 1,042
High-resolution TADs reveal DNA sequences underlying genome organization in flies
Ramírez, F., Bhardwaj, V., Arrigoni, L., Lam, K. C., Grüning, B. A., Villaveces, J. M., Habermann, B. H., Akhtar, A., & Manke, T. (2018) · Nature Communications · doi:10.1038/s41467-017-02525-w · Cited by 993
CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function
Guo, Y., Xu, Q., Canzio, D., Shou, J., Li, J., Gorkin, D. U., Jung, I., Wu, H., Zhai, Y., Tang, Y., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.038 · Cited by 958
Wutz, G., Várnai, C., Nagasaka, K., Cisneros, D. A., Stocsits, R. R., Tang, W., Schoenfelder, S., Jessberger, G., Muhar, M., Hossain, M. J., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201798004 · Cited by 864
Functional and Mechanistic Diversity of Distal Transcription Enhancers
Bulger, M., & Groudine, M. (2011) · Cell · doi:10.1016/j.cell.2011.01.024 · Cited by 803
CrossMap: a versatile tool for coordinate conversion between genome assemblies
Zhao, H., Sun, Z., Wang, J., Huang, H., Kocher, J., & Wang, L. (2013) · Bioinformatics · doi:10.1093/bioinformatics/btt730 · Cited by 760
Structural variation in the 3D genome
Spielmann, M., Lupiáñez, D. G., & Mundlos, S. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0007-0 · Cited by 752
fdrtool: a versatile R package for estimating local and tail area-based false discovery rates
Strimmer, K. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn209 · Cited by 723
CTCF 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
Phenotypic impact of genomic structural variation: insights from and for human disease
Weischenfeldt, J., Symmons, O., Spitz, F., & Korbel, J. O. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3373 · Cited by 674
Self-citationFormation of new chromatin domains determines pathogenicity of genomic duplications
Franke, M., Ibrahim, D. M., Andrey, G., Schwarzer, W., Heinrich, V., Schöpflin, R., Kraft, K., Kempfer, R., Jerković, I., Chan, W.-L., et al. (2016) · Nature · doi:10.1038/nature19800 · Cited by 673
Huang, W., Massouras, A., Inoue, Y., Peiffer, J., Ràmia, M., Tarone, A. M., Turlapati, L., Zichner, T., Zhu, D., Lyman, R. F., et al. (2014) · Genome Research · doi:10.1101/gr.171546.113 · Cited by 661
Self-citationEnhancer hijacking activates GFI1 family oncogenes in medulloblastoma
Northcott, P. A., Lee, C., Zichner, T., Stütz, A. M., Erkek, S., Kawauchi, D., Shih, D. J. H., Hovestadt, V., Zapatka, M., Sturm, D., et al. (2014) · Nature · doi:10.1038/nature13379 · Cited by 642
Self-citationDevelopmental enhancers and chromosome topology
Furlong, E. E. M., & Levine, M. (2018) · Science · doi:10.1126/science.aau0320 · Cited by 641
Self-citationCTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation
Narendra, V., Rocha, P. P., An, D., Raviram, R., Skok, J. A., Mazzoni, E. O., & Reinberg, D. (2015) · Science · doi:10.1126/science.1262088 · Cited by 535
Bonn, S., Zinzen, R. P., Girardot, C., Gustafson, E. H., Perez-Gonzalez, A., Delhomme, N., Ghavi-Helm, Y., Wilczyński, B., Riddell, A., & Furlong, E. E. M. (2012) · Nature Genetics · doi:10.1038/ng.1064 · Cited by 502
Self-citationTranscriptional Enhancers in Animal Development and Evolution
Levine, M. (2010) · Current Biology · doi:10.1016/j.cub.2010.06.070 · Cited by 468
CHiCAGO: robust detection of DNA looping interactions in Capture Hi-C data
Cairns, J., Freire-Pritchett, P., Wingett, S. W., Várnai, C., Dimond, A., Plagnol, V., Zerbino, D., Schoenfelder, S., Javierre, B.-M., Osborne, C., et al. (2016) · Genome Biology · doi:10.1186/s13059-016-0992-2 · Cited by 417
Combinatorial binding predicts spatio-temporal cis-regulatory activity
Zinzen, R. P., Girardot, C., Gagneur, J., Braun, M. M., & Furlong, E. E. M. (2009) · Nature · doi:10.1038/nature08531 · Cited by 404
Self-citationWeischenfeldt, J., Dubash, T., Drainas, A. P., Mardin, B. R., Chen, Y., Stütz, A. M., Waszak, S. M., Bosco, G., Halvorsen, A. R., Raeder, B., et al. (2017) · Nature Genetics · doi:10.1038/ng.3722 · Cited by 404
Self-citationUnified representation of genetic variants
Tan, A. K. S., Abecasis, G. R., & Kang, H. M. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv112 · Cited by 388
The cis-regulatory dynamics of embryonic development at single-cell resolution
Cusanovich, D. A., Reddington, J. P., Garfield, D. A., Daza, R. M., Aghamirzaie, D., Marco-Ferreres, R., Pliner, H. A., Christiansen, L., Qiu, X., Steemers, F. J., et al. (2018) · Nature · doi:10.1038/nature25981 · Cited by 363
Self-citationMultiplexed analysis of chromosome conformation at vastly improved sensitivity
Davies, J. O. J., Telenius, J. M., McGowan, S. J., Roberts, N. A., Taylor, S., Higgs, D. R., & Hughes, J. R. (2016) · Nature Methods · doi:10.1038/nmeth.3664 · Cited by 268
Creating a functional single-chromosome yeast
Shao, Y., Lü, N., Wu, Z., Cai, C., Wang, S., Zhang, L.-L., Zhou, F., Xiao, S., Liu, L., Zeng, X., et al. (2018) · Nature · doi:10.1038/s41586-018-0382-x · Cited by 261
Polycomb-Dependent Chromatin Looping Contributes to Gene Silencing during Drosophila Development
Ogiyama, Y., Schuettengruber, B., Papadopoulos, G. L., Chang, J., & Cavalli, G. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.05.032 · Cited by 248
Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome.
Shen, Y., Wang, Y., Chen, T., Gao, F., Gong, J., Abramczyk, D., Walker, R., Zhao, H., Chen, S., Liu, W., et al. (2017) · Science · doi:10.1126/science.aaf4791 · Cited by 202
Rodríguez-Carballo, E., Lopez‐Delisle, L., Zhan, Y., Fabre, P. J., Beccari, L. L., El-Idrissi, I., Huynh, T. H. N., Özadam, H., Dekker, J., & Duboule, D. (2017) · Genes & Development · doi:10.1101/gad.307769.117 · Cited by 180
Dynamic reprogramming of chromatin accessibility during Drosophilaembryo development
Thomas, S., Li, X., Sabo, P. J., Sandstrom, R. S., Thurman, R. E., Canfield, T. K., Giste, E., Fisher, W., Hammonds, A. S., Celniker, S., et al. (2011) · Genome biology · doi:10.1186/gb-2011-12-5-r43 · Cited by 176
A cell‐based model system links chromothripsis with hyperploidy
Mardin, B. R., Drainas, A. P., Waszak, S. M., Weischenfeldt, J., Isokane, M., Stütz, A. M., Raeder, B., Efthymiopoulos, T., Buccitelli, C., Segura‐Wang, M., et al. (2015) · Molecular Systems Biology · doi:10.15252/msb.20156505 · Cited by 144
Self-citationEnhancer-adoption as a mechanism of human developmental disease
Lettice, L. A., Daniels, S. L., Sweeney, E., Venkataraman, S., Devenney, P. S., Gautier, P. E., Morrison, H., Fantes, J. A., Hill, R. E., & FitzPatrick, D. R. (2011) · Human Mutation · doi:10.1002/humu.21615 · Cited by 111
Zichner, T., Garfield, D. A., Rausch, T., Stütz, A. M., Cannavò, E., Braun, M. M., Furlong, E. E. M., & Korbel, J. O. (2012) · Genome Research · doi:10.1101/gr.142646.112 · Cited by 78
Self-citationTsujimura, T., Klein, F. A., Langenfeld, K., Glaser, J., Huber, W. K., & Spitz, F. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1004897 · Cited by 64
Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster
Lee, H., Cho, D.-Y., Whitworth, C., Eisman, R. C., Phelps, M., Roote, J., Kaufman, T. C., Cook, K. R., Russell, S. R. H., Przytycka, T. M., et al. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006295 · Cited by 41
Miller, D. E., Cook, K. R., Arvanitakis, A. V., & Hawley, R. S. (2016) · G3 Genes Genomes Genetics · doi:10.1534/g3.116.029330 · Cited by 33
Neighbourhood Continuity Is Not Required for Correct Testis Gene Expression in Drosophila
Meadows, L. A., Chan, Y. S., Roote, J., & Russell, S. R. H. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000552 · Cited by 30
The Molecular and Genetic Characterization of Second Chromosome Balancers in Drosophila melanogaster
Miller, D. E., Cook, K. R., Hemenway, E. A., Fang, V., Miller, A. L., Hales, K. G., & Hawley, R. S. (2018) · G3 Genes Genomes Genetics · doi:10.1534/g3.118.200021 · Cited by 18
Research works printed but not linked: 4
- Oster, I. I. A new crossing-over suppressor in chromosome 2 effective in the presence of heterologous inversions. Drosophila Inform. Serv. 30, 145 (1956).
- Tinderholt, V. New mutants report. Drosophila Inform. Serv. 34, 53–54 (1960).
- Li, H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. Preprint at https://arxiv.org/abs/1303.3997 (2013). · arXiv
- Garrison, E. & Marth, G. Haplotype-based variant detection from short-read sequencing. Preprint at https://arxiv.org/abs/1207.3907 (2012). · arXiv
Cited by
Sorted by citations
The Self-Organizing Genome: Principles of Genome Architecture and Function
Misteli, T. (2020) · Cell · doi:10.1016/j.cell.2020.09.014 · Cited by 742
Nonlinear control of transcription through enhancer–promoter interactions
Zuin, J., Roth, G., Zhan, Y., Cramard, J., Redolfi, J., Piskadlo, E., Mach, P., Kryzhanovska, M., Tihanyi, G., Kohler, H., et al. (2022) · Nature · doi:10.1038/s41586-022-04570-y · Cited by 415
Advances in Targeting ‘Undruggable’ transcription Factors With Small Molecules
Henley, M. J., & Koehler, A. N. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00199-0 · Cited by 409
Towards a comprehensive catalogue of validated and target-linked human enhancers
Gasperini, M., Tome, J. M., & Shendure, J. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-019-0209-0 · Cited by 396
Understanding 3D genome organization by multidisciplinary methods
Jerković, I., & Cavalli, G. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00362-w · Cited by 413
Metadata
- Authors
- Ghavi-Helm, Y., Jankowski, A., Meiers, S., Viales, R. R., Korbel, J. O., & Furlong, E. E. M.
- Affiliations
- Lyon 1 Université (FR)
- European Molecular Biology Laboratory (DE)
- Corresponding author
- Ghavi-Helm, Yad
- Korbel, Jan O.
- Furlong, Eileen E. M.
- ORCID
- Venue
- Nature Genetics
- Published
- 2019-07-15
- Volume
- 51
- Issue
- 8
- Pages
- 1272-1282
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC7116017
- OpenAlex
- W2958578938
- Cited by
- 354
- References
- 57
- Citations by year
- 2026: 16 · 2025: 33 · 2024: 41 · 2023: 54 · 2022: 60 · 2021: 74 · 2020: 56 · 2019: 19
- FWCI
- 17.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- Nature
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- chromatin topology, gene expression, balancer chromosomes, chromosomal inversions, topologically associating domains, enhancer-promoter interactions, cis effect, Drosophila, chromosomal duplication, chromosomal deletion
- MeSH terms
- Animals, Chromatin, Chromosome Mapping, Drosophila melanogaster, Enhancer Elements, Genetic, Female, Gene Expression Regulation, Male, Promoter Regions, Genetic, Gene Rearrangement, Genome, Insect, Chromosomes, Insect
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
