Cited by 388Genomics and Chromatin DynamicsChromosomal and Genetic VariationsNuclear Structure and Function

Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains

Open access
Ulianov, Sergey V., Khrameeva, Ekaterina E., Gavrilov, Alexey A., Flyamer, Ilya M., Kos, Pavel, Mikhaleva, Elena A., Penin, Aleksey A., Logacheva, Maria D. +5 more·2016·Genome Research

Abstract

Recent advances enabled by the Hi-C technique have unraveled many principles of chromosomal folding that were subsequently linked to disease and gene regulation. In particular, Hi-C revealed that chromosomes of animals are organized into topologically associating domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression. Mechanisms that underlie partitioning of the genome into TADs remain poorly understood. To explore principles of TAD folding in Drosophila melanogaster , we performed Hi-C and poly(A) + RNA-seq in four cell lines of various origins (S2, Kc167, DmBG3-c2, and OSC). Contrary to previous studies, we find that regions between TADs (i.e., the inter-TADs and TAD boundaries) in Drosophila are only weakly enriched with the insulator protein dCTCF, while another insulator protein Su(Hw) is preferentially present within TADs. However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. Accordingly, we find that binding of insulator proteins dCTCF and Su(Hw) predicts TAD boundaries much worse than active chromatin marks do. Interestingly, inter-TADs correspond to decompacted inter-bands of polytene chromosomes, whereas TADs mostly correspond to densely packed bands. Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin. We propose the mechanism of TAD self-assembly based on the ability of nucleosomes from inactive chromatin to aggregate, and lack of this ability in acetylated nucleosomal arrays. Finally, we test this hypothesis by polymer simulations and find that TAD partitioning may be explained by different modes of inter-nucleosomal interactions for active and inactive chromatin.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/gr.196006.115

Cites

12 of 12 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • It has been proposed that Drosophila TADs are formed by condensation of nucleosomes and thus should be rather called 'compartmental domains'.

    “It has been proposed that Drosophila TADs are formed by condensation of nucleosomes [123] and thus should be rather called “compartmental domains” [124].”

    From Enhancer Function in the 3D Genome (2023) · cites this paper as [123]

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

Flagged first, then by citations

Research works printed but not linked: 74

  1. Ahanger SH, Gunther K, Weth O, Bartkuhn M, Bhonde RR, Shouche YS, Renkawitz R. 2014 Ectopically tethered CP190 induces large-scale chromatin decondensation. Sci Rep 4: 3917. 24472778 PMC3905270
  2. Akhtar A, Becker PB. 2000 Activation of transcription through histone H4 acetylation by MOF, an acetyltransferase essential for dosage compensation in Drosophila. Mol Cell 5: 367– 375. 10882077
  3. Allahverdi A, Yang R, Korolev N, Fan Y, Davey CA, Liu CF, Nordenskiold L. 2011 The effects of histone H4 tail acetylations on cation-induced chromatin folding and self-association. Nucleic Acids Res 39: 1680– 1691. 21047799 PMC3061077
  4. Barbieri M, Chotalia M, Fraser J, Lavitas LM, Dostie J, Pombo A, Nicodemi M. 2012 Complexity of chromatin folding is captured by the strings and binders switch model. Proc Natl Acad Sci 109: 16173– 16178. 22988072 PMC3479593
  5. Bartkuhn M, Straub T, Herold M, Herrmann M, Rathke C, Saumweber H, Gilfillan GD, Becker PB, Renkawitz R. 2009 Active promoters and insulators are marked by the centrosomal protein 190. EMBO J 28: 877– 888. 19229299 PMC2670862
  6. Belton JM, McCord RP, Gibcus JH, Naumova N, Zhan Y, Dekker J. 2012 Hi-C: a comprehensive technique to capture the conformation of genomes. Methods 58: 268– 276. 22652625 PMC3874846
  7. Benedetti F, Dorier J, Burnier Y, Stasiak A. 2014 Models that include supercoiling of topological domains reproduce several known features of interphase chromosomes. Nucleic Acids Res 42: 2848– 2855. 24366878 PMC3950722
  8. Berlivet S, Paquette D, Dumouchel A, Langlais D, Dostie J, Kmita M. 2013 Clustering of tissue-specific sub-TADs accompanies the regulation of HoxA genes in developing limbs. PLoS Genet 9: e1004018. 24385922 PMC3873244
  9. Brown JB, Boley N, Eisman R, May GE, Stoiber MH, Duff MO, Booth BW, Wen J, Park S, Suzuki AM, 2014 Diversity and dynamics of the Drosophila transcriptome. Nature 512: 393– 399. 24670639 PMC4152413
  10. Celniker SE, Dillon LA, Gerstein MB, Gunsalus KC, Henikoff S, Karpen GH, Kellis M, Lai EC, Lieb JD, MacAlpine DM, 2009 Unlocking the secrets of the genome. Nature 459: 927– 930. 19536255 PMC2843545
  11. Chen K, Wallis JW, McLellan MD, Larson DE, Kalicki JM, Pohl CS, McGrath SD, Wendl MC, Zhang Q, Locke DP, 2009 BreakDancer: an algorithm for high-resolution mapping of genomic structural variation. Nat Methods 6: 677– 681. 19668202 PMC3661775
  12. Chertovich A, Kos P. 2014 Crumpled globule formation during collapse of a long flexible and semiflexible polymer in poor solvent. J Chem Phys 141: 134903. 25296833
  13. Cremer T, Cremer C. 2001 Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2: 292– 301. 11283701
  14. de Graaf CA, van Steensel B. 2013 Chromatin organization: form to function. Curr Opin Genet Dev 23: 185– 190. 23274160
  15. Duan Z, Andronescu M, Schutz K, McIlwain S, Kim YJ, Lee C, Shendure J, Fields S, Blau CA, Noble WS. 2011 A three-dimensional model of the yeast genome. Nature 465: 363– 367. 20436457 PMC2874121
  16. Echalier G, Ohanessian A. 1969 [Isolation, in tissue culture, of Drosophila melangaster cell lines]. C R Acad Sci Hebd Seances Acad Sci D 268: 1771– 1773. 4976834
  17. Feng S, Cokus SJ, Schubert V, Zhai J, Pellegrini M, Jacobsen SE. 2014 Genome-wide Hi-C analyses in wild-type and mutants reveal high-resolution chromatin interactions in Arabidopsis. Mol Cell 55: 694– 707. 25132175 PMC4347903
  18. Fierz B, Chatterjee C, McGinty RK, Bar-Dagan M, Raleigh DP, Muir TW. 2011 Histone H2B ubiquitylation disrupts local and higher-order chromatin compaction. Nat Chem Biol 7: 113– 119. 21196936 PMC3078768
  19. Filion GJ, van Bemmel JG, Braunschweig U, Talhout W, Kind J, Ward LD, Brugman W, de Castro IJ, Kerkhoven RM, Bussemaker HJ, 2010 Systematic protein location mapping reveals five principal chromatin types in Drosophila cells. Cell 143: 212– 224. 20888037 PMC3119929
  20. Filippova D, Patro R, Duggal G, Kingsford C. 2014 Identification of alternative topological domains in chromatin. Algorithms Mol Biol 9: 14. 24868242 PMC4019371
  21. Fudenberg G, Mirny LA. 2012 Higher-order chromatin structure: bridging physics and biology. Curr Opin Genet Dev 22: 115– 124. 22360992 PMC3697851
  22. Gavrilov AA, Kudryavtsev YV, Chertovich AV. 2013 Phase diagrams of block copolymer melts by dissipative particle dynamics simulations. J Chem Phys 139: 224901. 24329087
  23. Gibcus JH, Dekker J. 2013 The hierarchy of the 3D genome. Mol Cell 49: 773– 782. 23473598 PMC3741673
  24. Gilfillan GD, Straub T, de Wit E, Greil F, Lamm R, van Steensel B, Becker PB. 2006 Chromosome-wide gene-specific targeting of the Drosophila dosage compensation complex. Genes Dev 20: 858– 870. 16547172 PMC1475731
  25. Gohl D, Aoki T, Blanton J, Shanower G, Kappes G, Schedl P. 2011 Mechanism of chromosomal boundary action: roadblock, sink, or loop? Genetics 187: 731– 748. 21196526 PMC3063668
  26. Graveley BR, Brooks AN, Carlson JW, Duff MO, Landolin JM, Yang L, Artieri CG, van Baren MJ, Boley N, Booth BW, 2011 The developmental transcriptome of Drosophila melanogaster. Nature 471: 473– 479. 21179090 PMC3075879
  27. Grob S, Schmid MW, Grossniklaus U. 2014 Hi-C analysis in Arabidopsis identifies the KNOT, a structure with similarities to the flamenco locus of Drosophila. Mol Cell 55: 678– 693. 25132176
  28. Hizume K, Yoshimura SH, Takeyasu K. 2005 Linker histone H1 per se can induce three-dimensional folding of chromatin fiber. Biochemistry 44: 12978– 12989. 16185066
  29. Holwerda SJ, de Laat W. 2013 CTCF: the protein, the binding partners, the binding sites and their chromatin loops. Philos Trans R Soc Lond B Biol Sci 368: 20120369. 23650640 PMC3682731
  30. Hou C, Li L, Qin ZS, Corces VG. 2012 Gene density, transcription, and insulators contribute to the partition of the Drosophila genome into physical domains. Mol Cell 48: 471– 484. 23041285 PMC3496039
  31. Jiang N, Emberly E, Cuvier O, Hart CM. 2009 Genome-wide mapping of boundary element-associated factor (BEAF) binding sites in Drosophila melanogaster links BEAF to transcription. Mol Cell Biol 29: 3556– 3568. 19380483 PMC2698748
  32. Jost D, Carrivain P, Cavalli G, Vaillant C. 2014 Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains. Nucleic Acids Res 42: 9553– 9561. 25092923 PMC4150797
  33. Kalashnikova AA, Porter-Goff ME, Muthurajan UM, Luger K, Hansen JC. 2013 The role of the nucleosome acidic patch in modulating higher order chromatin structure. J R Soc Interface 10: 20121022. 23446052 PMC3627075
  34. Kharchenko PV, Alekseyenko AA, Schwartz YB, Minoda A, Riddle NC, Ernst J, Sabo PJ, Larschan E, Gorchakov AA, Gu T, 2011 Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature 471: 480– 485. 21179089 PMC3109908
  35. Khrameeva EE, Mironov AA, Fedonin GG, Khaitovich P, Gelfand MS. 2012 Spatial proximity and similarity of the epigenetic state of genome domains. PLoS One 7: e33947. 22496774 PMC3319547
  36. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. 2013 TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 14: R36. 23618408 PMC4053844
  37. Kind J, Vaquerizas JM, Gebhardt P, Gentzel M, Luscombe NM, Bertone P, Akhtar A. 2008 Genome-wide analysis reveals MOF as a key regulator of dosage compensation and gene expression in Drosophila. Cell 133: 813– 828. 18510926
  38. Kolbl AC, Weigl D, Mulaw M, Thormeyer T, Bohlander SK, Cremer T, Dietzel S. 2012 The radial nuclear positioning of genes correlates with features of megabase-sized chromatin domains. Chromosome Res 20: 735– 752. 23053570
  39. Langmead B, Salzberg SL. 2012 Fast gapped-read alignment with Bowtie 2. Nat Methods 9: 357– 359. 22388286 PMC3322381
  40. Le TB, Imakaev MV, Mirny LA, Laub MT. 2013 High-resolution mapping of the spatial organization of a bacterial chromosome. Science 342: 731– 734. 24158908 PMC3927313
  41. Lemieux JE, Kyes SA, Otto TD, Feller AI, Eastman RT, Pinches RA, Berriman M, Su XZ, Newbold CI. 2013 Genome-wide profiling of chromosome interactions in Plasmodium falciparum characterizes nuclear architecture and reconfigurations associated with antigenic variation. Mol Microbiol 90: 519– 537. 23980881 PMC3894959
  42. Li X, Wang S, Li Y, Deng C, Steiner LA, Xiao H, Wu C, Bungert J, Gallagher PG, Felsenfeld G, 2011 Chromatin boundaries require functional collaboration between the hSET1 and NURF complexes. Blood 118: 1386– 1394. 21653943 PMC3152501
  43. Li L, Lyu X, Hou C, Takenaka N, Nguyen HQ, Ong CT, Cubenas-Potts C, Hu M, Lei EP, Bosco G, 2015 Widespread rearrangement of 3D chromatin organization underlies polycomb-mediated stress-induced silencing. Mol Cell 58: 216– 231. 25818644 PMC4402144
  44. Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO, 2009 Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326: 289– 293. 19815776 PMC2858594
  45. Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ. 1997 Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389: 251– 260. 9305837
  46. McCarthy DJ, Chen Y, Smyth GK. 2012 Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res 40: 4288– 4297. 22287627 PMC3378882
  47. Mirny LA. 2011 The fractal globule as a model of chromatin architecture in the cell. Chromosome Res 19: 37– 51. 21274616 PMC3040307
  48. Mizuguchi T, Fudenberg G, Mehta S, Belton JM, Taneja N, Folco HD, FitzGerald P, Dekker J, Mirny L, Barrowman J, 2014 Cohesin-dependent globules and heterochromatin shape 3D genome architecture in S. pombe. Nature 516: 432– 435. 25307058 PMC4465753
  49. Mukhopadhyay S, Schedl P, Studitsky VM, Sengupta AM. 2011 Theoretical analysis of the role of chromatin interactions in long-range action of enhancers and insulators. Proc Natl Acad Sci 108: 19919– 19924. 22123989 PMC3250180
  50. Mutskov VJ, Farrell CM, Wade PA, Wolffe AP, Felsenfeld G. 2002 The barrier function of an insulator couples high histone acetylation levels with specific protection of promoter DNA from methylation. Genes Dev 16: 1540– 1554. 12080092 PMC186352
  51. Niki Y, Yamaguchi T, Mahowald AP. 2006 Establishment of stable cell lines of Drosophila germ-line stem cells. Proc Natl Acad Sci 103: 16325– 16330. 17056713 PMC1637581
  52. Pepenella S, Murphy KJ, Hayes JJ. 2014 Intra- and inter-nucleosome interactions of the core histone tail domains in higher-order chromatin structure. Chromosoma 123: 3– 13. 23996014 PMC3938996
  53. Pope BD, Ryba T, Dileep V, Yue F, Wu W, Denas O, Vera DL, Wang Y, Hansen RS, Canfield TK, 2014 Topologically associating domains are stable units of replication-timing regulation. Nature 515: 402– 405. 25409831 PMC4251741
  54. Ramírez F, Lingg T, Toscano S, Lam KC, Georgiev P, Chung HR, Lajoie BR, de Wit E, Zhan Y, de Laat W, 2015 High-affinity sites form an interaction network to facilitate spreading of the MSL complex across the X chromosome in Drosophila. Mol Cell 60: 146– 162. 26431028 PMC4806858
  55. Rao SS, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, Sanborn AL, Machol I, Omer AD, Lander ES, 2014 A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159: 1665– 1680. 25497547 PMC5635824
  56. Rausch T, Zichner T, Schlattl A, Stutz AM, Benes V, Korbel JO. 2012 DELLY: structural variant discovery by integrated paired-end and split-read analysis. Bioinformatics 28: i333– i339. 22962449 PMC3436805
  57. Ricci MA, Manzo C, Garcia-Parajo MF, Lakadamyali M, Cosma MP. 2015 Chromatin fibers are formed by heterogeneous groups of nucleosomes in vivo. Cell 160: 1145– 1158. 25768910
  58. Schalch T, Duda S, Sargent DF, Richmond TJ. 2005 X-ray structure of a tetranucleosome and its implications for the chromatin fibre. Nature 436: 138– 141. 16001076
  59. Schneider I. 1972 Cell lines derived from late embryonic stages of Drosophila melanogaster. J Embryol Exp Morphol 27: 353– 365. 4625067
  60. Sexton T, Yaffe E, Kenigsberg E, Bantignies F, Leblanc B, Hoichman M, Parrinello H, Tanay A, Cavalli G. 2012 Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148: 458– 472. 22265598
  61. Shahbazian MD, Grunstein M. 2007 Functions of site-specific histone acetylation and deacetylation. Annu Rev Biochem 76: 75– 100. 17362198
  62. Shogren-Knaak M, Ishii H, Sun JM, Pazin MJ, Davie JR, Peterson CL. 2006 Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science 311: 844– 847. 16469925
  63. Sinha D, Shogren-Knaak MA. 2010 Role of direct interactions between the histone H4 Tail and the H2A core in long range nucleosome contacts. J Biol Chem 285: 16572– 16581. 20351095 PMC2878085
  64. Smeets D, Markaki Y, Schmid VJ, Kraus F, Tattermusch A, Cerase A, Sterr M, Fiedler S, Demmerle J, Popken J, 2014 Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci. Epigenetics Chromatin 7: 8. 25057298 PMC4108088
  65. Splinter E, Heath H, Kooren J, Palstra RJ, Klous P, Grosveld F, Galjart N, de Laat W. 2006 CTCF mediates long-range chromatin looping and local histone modification in the β-globin locus. Genes Dev 20: 2349– 2354. 16951251 PMC1560409
  66. Thomas JO, Stott K. 2012 H1 and HMGB1: modulators of chromatin structure. Biochem Soc Trans 40: 341– 346. 22435809
  67. Tolhuis B, Blom M, Kerkhoven RM, Pagie L, Teunissen H, Nieuwland M, Simonis M, de Laat W, van Lohuizen M, van Steensel B. 2011 Interactions among Polycomb domains are guided by chromosome architecture. PLoS Genet 7: e1001343. 21455484 PMC3063757
  68. Ui K, Nishihara S, Sakuma M, Togashi S, Ueda R, Miyata Y, Miyake T. 1994 Newly established cell lines from Drosophila larval CNS express neural specific characteristics. In Vitro Cell Dev Biol Anim 30A: 209– 216. 8069443
  69. Van Bortle K, Nichols MH, Li L, Ong CT, Takenaka N, Qin ZS, Corces VG. 2014 Insulator function and topological domain border strength scale with architectural protein occupancy. Genome Biol 15: R82. 24981874 PMC4226948
  70. Vatolina TY, Boldyreva LV, Demakova OV, Demakov SA, Kokoza EB, Semeshin VF, Babenko VN, Goncharov FP, Belyaeva ES, Zhimulev IF. 2011 Identical functional organization of nonpolytene and polytene chromosomes in Drosophila melanogaster. PLoS One 6: e25960. 22022482 PMC3191165
  71. Williamson I, Berlivet S, Eskeland R, Boyle S, Illingworth RS, Paquette D, Dostie J, Bickmore WA. 2014 Spatial genome organization: contrasting views from chromosome conformation capture and fluorescence in situ hybridization. Genes Dev 28: 2778– 2791. 25512564 PMC4265680
  72. Wood AM, Van Bortle K, Ramos E, Takenaka N, Rohrbaugh M, Jones BC, Jones KC, Corces VG. 2011 Regulation of chromatin organization and inducible gene expression by a Drosophila insulator. Mol Cell 44: 29– 38. 21981916 PMC3190163
  73. Zabidi MA, Arnold CD, Schernhuber K, Pagani M, Rath M, Frank O, Stark A. 2015 Enhancer-core-promoter specificity separates developmental and housekeeping gene regulation. Nature 518: 556– 559. 25517091 PMC6795551
  74. Zhimulev IF, Zykova TY, Goncharov FP, Khoroshko VA, Demakova OV, Semeshin VF, Pokholkova GV, Boldyreva LV, Demidova DS, Babenko VN, 2014 Genetic organization of interphase chromosome bands and interbands in Drosophila melanogaster. PLoS One 9: e101631. 25072930 PMC4114487

Cited by

Sorted by citations

Authors
Ulianov, S. V., Khrameeva, E. E., Gavrilov, A. A., Flyamer, I. M., Kos, P., Mikhaleva, E. A., Penin, A. A., Logacheva, M. D., Imakaev, M. V., Chertovich, A., Gelfand, M. S., Shevelyov, Y. Y., & Razin, S. V.
Affiliations
  • Lomonosov Moscow State University (RU)
  • Skolkovo Institute of Science and Technology (RU)
  • Russian Academy of Sciences (RU)
  • Institute of Molecular Genetics (RU)
  • Massachusetts Institute of Technology (US)
Corresponding author
Razin, Sergey V.
Venue
Genome Research
Published
2015-10-30
Volume
26
Issue
1
Pages
70-84
ISSN
  • 1088-9051 (ISSN-L)
  • 1549-5469
OpenAlex
W2172400873
Cited by
388
References
12
Citations by year
2026: 12 · 2025: 20 · 2024: 31 · 2023: 25 · 2022: 34 · 2021: 50 · 2020: 50 · 2019: 38 · 2018: 55 · 2017: 42 · 2016: 28 · 2015: 3
Type
posted content
Language
en
Open access
Locations
  • Genome Research (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Russian Foundation for Basic Research (13-00-40086-K, 14-04-91331, 14-04-00010, 14-03-00825)
  • Presidium of the Russian Academy of Sciences
  • Russian Science Foundation (14-14-01088, 14-24-00155)
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 › Nuclear Structure and Function
Keywords
topologically associating domains, chromosome segregation, chromatin folding, insulator proteins, Su(Hw), active chromatin, TAD boundaries, polytene chromosomes, nucleosome compaction, chromatin acetylation, Drosophila melanogaster, gene expression regulation
MeSH terms
Animals, Cell Line, Chromatin, Chromosome Mapping, Computer Simulation, Drosophila melanogaster, Models, Molecular, Nucleosomes, Transcription, Genetic, Sequence Analysis, RNA, Chromatin Assembly and Disassembly, Genome, Insect, Polytene Chromosomes

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