Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation
Abstract
DNA methylation is an epigenetic modification associated with transcriptional repression of promoters and is essential for mammalian development. Establishment of DNA methylation is mediated by the de novo DNA methyltransferases DNMT3A and DNMT3B, whereas DNMT1 ensures maintenance of methylation through replication. Absence of these enzymes is lethal, and somatic mutations in these genes have been associated with several human diseases. How genomic DNA methylation patterns are regulated remains poorly understood, as the mechanisms that guide recruitment and activity of DNMTs in vivo are largely unknown. To gain insights into this matter we determined genomic binding and site-specific activity of the mammalian de novo DNA methyltransferases DNMT3A and DNMT3B. We show that both enzymes localize to methylated, CpG-dense regions in mouse stem cells, yet are excluded from active promoters and enhancers. By specifically measuring sites of de novo methylation, we observe that enzymatic activity reflects binding. De novo methylation increases with CpG density, yet is excluded from nucleosomes. Notably, we observed selective binding of DNMT3B to the bodies of transcribed genes, which leads to their preferential methylation. This targeting to transcribed sequences requires SETD2-mediated methylation of lysine 36 on histone H3 and a functional PWWP domain of DNMT3B. Together these findings reveal how sequence and chromatin cues guide de novo methyltransferase activity to ensure methylome integrity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
High levels of DNA methylation on intragenic CGIs are consistent with high levels of DNMT3B binding on intragenic CGIs.
“As DNMT3B regulates intragenic DNA methylation levels54, high levels of DNA methylation levels are consistent with high levels of DNMT3B binding on intragenic CGIs”
From Alternative promoters in CpG depleted regions are prevalently associated with epigenetic misregulation of liver cancer transcriptomes (2023) · cites this paper as [54]
Establishment of intragenic 5mC is a controlled process carried out by DNMT3B and the co-transcriptionally regulated histone modification H3K36me.
“Studies with mESC and a heterologous yeast system found that the establishment of intragenic 5mC is a controlled process carried out by de novo DNA methyltransferase DNMT3B and co-transcriptionally regulated histone modification H3K36me (32, 33).”
From Dynamic DNA methylation: In the right place at the right time (2018) · cites this paper as [32]
Interaction between DNMT3B and H3K36me leads to higher levels of intragenic 5mC for active genes in mouse embryonic stem cells.
“The interaction between DNMT3B and H3K36me leads to greater levels of intragenic 5mC for active genes in mESC (32).”
From Dynamic DNA methylation: In the right place at the right time (2018) · cites this paper as [32]
Functional analyses of 5mC have traditionally relied on pharmacological or genetic perturbations that affect 5mC levels genome-wide.
“Functional analyses of 5mC have traditionally relied on pharmacological or genetic perturbations that affect 5mC levels genome-wide (30, 32).”
From Dynamic DNA methylation: In the right place at the right time (2018) · cites this paper as [32]
Cites
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849 · see citing works
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581 · see citing works
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339 · see citing works
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 · see citing works
Okano, M., Bell, D. W., Haber, D. A., & Li, E. (1999) · Cell · doi:10.1016/s0092-8674(00)81656-6 · Cited by 6,143 · see citing works
Functions of DNA methylation: islands, start sites, gene bodies and beyond
Jones, P. A. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3230 · Cited by 6,061 · see citing works
DNA targeting specificity of RNA-guided Cas9 nucleases
Hsu, P. D., Scott, D. A., Weinstein, J. A., Ran, F. A., Konermann, S., Agarwala, V., Li, Y., Fine, E. J., Wu, X., Shalem, O., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2647 · Cited by 4,741 · see citing works
Software for Computing and Annotating Genomic Ranges
Lawrence, M. F., Huber, W. K., Pagès, H., Aboyoun, P., Carlson, M. R. J., Gentleman, R. C., Morgan, M. T., & Carey, V. J. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003118 · Cited by 4,438 · see citing works
DNA methylation: roles in mammalian development
Smith, Z. D., & Meissner, A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3354 · Cited by 3,045 · see citing works
DNA methylation landscapes: Provocative insights from epigenomics
Suzuki, M. M., & Bird, A. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2341 · Cited by 3,039 · see citing works
EUKARYOTIC CYTOSINE METHYLTRANSFERASES
Goll, M. G., & Bestor, T. H. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.010904.153721 · Cited by 2,066 · see citing works
Genome-Wide Evolutionary Analysis of Eukaryotic DNA Methylation
Zemach, A., McDaniel, I. E., Silva, P., & Zilberman, D. (2010) · Science · doi:10.1126/science.1186366 · Cited by 1,796 · see citing works
DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA
Ooi, S. K. T., Qiu, C., Bernstein, E., Li, K., Jia, D., Yang, Z., Erdjument‐Bromage, H., Tempst, P., Lin, S., Allis, C. D., et al. (2007) · Nature · doi:10.1038/nature05987 · Cited by 1,558 · see citing works
DNA-binding factors shape the mouse methylome at distal regulatory regions
Stadler, M. B., Murr, R., Burger, L., Ivanek, R., Lienert, F., Schöler, A., Nimwegen, E. V., Wirbelauer, C., Oakeley, E. J., Gaidatzis, D., et al. (2011) · Nature · doi:10.1038/nature10716 · Cited by 1,383 · see citing works
Self-citationPROMALS3D: a tool for multiple protein sequence and structure alignments
Pei, J., Kim, B., & Grishin, N. V. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn072 · Cited by 1,269 · see citing works
Xu, G., Bestor, T. H., Bourc’his, D., Hsieh, C., Tommerup, N., Bugge, M., Hultén, M. A., Qu, X., Russo, J. J., & Viégas-Pèquignot, E. (1999) · Nature · doi:10.1038/46052 · Cited by 1,204 · see citing works
Gene Body Methylation Can Alter Gene Expression and Is a Therapeutic Target in Cancer
Yang, X., Han, H., De Carvalho, D. D., Lay, F. D., Jones, P. A., & Liang, G. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.07.028 · Cited by 1,199 · see citing works
The Transcriptional and Epigenomic Foundations of Ground State Pluripotency
Marks, H., Kalkan, T., Menafra, R., Denissov, S., Jones, K. A., Hofemeister, H., Nichols, J., Kranz, A., Stewart, A., Smith, A. G., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.026 · Cited by 881 · see citing works
Yan, X., Xu, J., Gu, Z., Pan, C., Lü, G., Shen, Y., Shi, J., Zhu, Y., Tang, L., Zhang, X., et al. (2011) · Nature Genetics · doi:10.1038/ng.788 · Cited by 806 · see citing works
Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells
Pastor, W. A., Pape, U. J., Huang, Y., Henderson, H. R., Lister, R., Ko, M., McLoughlin, E. M., Brudno, Y., Mahapatra, S., Kapranov, P., et al. (2011) · Nature · doi:10.1038/nature10102 · Cited by 804 · see citing works
Chen, T., Ueda, Y., Dodge, J. E., Wang, Z., & Li, E. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.16.5594-5605.2003 · Cited by 751 · see citing works
Dynamic CpG island methylation landscape in oocytes and preimplantation embryos
Smallwood, S. A., Tomizawa, S.-I., Krueger, F., Ruf, N., Carli, N., Segonds-Pichon, A., Sato, S., Hata, K., Andrews, S., & Kelsey, G. (2011) · Nature Genetics · doi:10.1038/ng.864 · Cited by 701 · see citing works
Krogan, N. J., Kim, M., Tong, A. H. Y., Golshani, A., Cagney, G., Canadien, V., Richards, D. P., Beattie, B. K., Emili, A., Boone, C. M., et al. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.12.4207-4218.2003 · Cited by 680 · see citing works
The Dnmt3a PWWP Domain Reads Histone 3 Lysine 36 Trimethylation and Guides DNA Methylation
Dhayalan, A., Rajavelu, A., Rathert, P., Tamas, R., Jurkowska, R. Z., Ragozin, S., & Jeltsch, A. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.089433 · Cited by 560 · see citing works
Tsumura, A., Hayakawa, T., Kumaki, Y., Takebayashi, S., Sakaue, M., Matsuoka, C., Shimotohno, K., Ishikawa, F., Li, E., Ueda, H. R., et al. (2006) · Genes to Cells · doi:10.1111/j.1365-2443.2006.00984.x · Cited by 544 · see citing works
Polycomb-Dependent H3K27me1 and H3K27me2 Regulate Active Transcription and Enhancer Fidelity
Ferrari, K. J., Scelfo, A., Jammula, S., Cuomo, A., Barozzi, I., Stützer, A., Fischle, W., Bonaldi, T., & Pasini, D. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.10.030 · Cited by 516 · see citing works
Genome-wide mapping of nucleosome positioning and DNA methylation within individual DNA molecules
Kelly, T. K., Liu, Y., Lay, F. D., Liang, G., Berman, B. P., & Jones, P. A. (2012) · Genome Research · doi:10.1101/gr.143008.112 · Cited by 455 · see citing works
Bachman, K. E., Rountree, M. R., & Baylin, S. B. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104661200 · Cited by 438 · see citing works
Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing
Hovestadt, V., Jones, D. T. W., Picelli, S., Wang, W., Kool, M., Northcott, P., Sultan, M., Stachurski, K., Ryzhova, M., Warnatz, H., et al. (2014) · Nature · doi:10.1038/nature13268 · Cited by 437 · see citing works
Methylation-Dependent and -Independent Genomic Targeting Principles of the MBD Protein Family
Baubec, T., Ivánek, R., Lienert, F., & Schübeler, D. (2013) · Cell · doi:10.1016/j.cell.2013.03.011 · Cited by 365 · see citing works
Self-citationgenomation: a toolkit to summarize, annotate and visualize genomic intervals
Akalin, A., Franke, V., Vlahoviček, K., Mason, C. E., & Schübeler, D. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu775 · Cited by 357 · see citing works
Self-citationZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression
Wen, H., Li, Y., Xi, Y., Jiang, S., Stratton, S. A., Peng, D., Tanaka, K. Y., Ren, Y.-F., Xia, Z., Wu, J., et al. (2014) · Nature · doi:10.1038/nature13045 · Cited by 344 · see citing works
Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease
Gilsbach, R., Preißl, S., Grüning, B. A., Schnick, T., Burger, L., Beneš, V., Würch, A., Bönisch, U., Günther, S., Backofen, R., et al. (2014) · Nature Communications · doi:10.1038/ncomms6288 · Cited by 319 · see citing works
Self-citationMethylation of genomes and genes at the invertebrate-vertebrate boundary
Tweedie, S., Charlton, J., Clark, V. H., & Bird, A. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.3.1469 · Cited by 293 · see citing works
Bibel, M., Richter, J., Lacroix, E., & Barde, Y.-A. (2007) · Nature Protocols · doi:10.1038/nprot.2007.147 · Cited by 283 · see citing works
Chen, T., Tsujimoto, N., & Li, E. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.20.9048-9058.2004 · Cited by 273 · see citing works
The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds
Qiu, C., Sawada, K., Zhang, X., & Cheng, X. (2002) · Nature Structural Biology · doi:10.1038/nsb759 · Cited by 261 · see citing works
Genome-wide nucleosome positioning during embryonic stem cell development
Teif, V. B., Vainshtein, Y., Caudron-Herger, M., Mallm, J.-P., Marth, C., Höfer, T., & Rippe, K. (2012) · Nature Structural &Molecular Biology · doi:10.1038/nsmb.2419 · Cited by 260 · see citing works
Molecular basis of histone H3K36me3 recognition by the PWWP domain of Brpf1
Vezzoli, A., Bonadies, N., Allen, M. D., Freund, S. M. V., Santiveri, C. M., Kvinlaug, B. T., Huntly, B. J. P., Göttgens, B., & Bycroft, M. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1797 · Cited by 218 · see citing works
Selective Anchoring of DNA Methyltransferases 3A and 3B to Nucleosomes Containing Methylated DNA
Jeong, S., Liang, G., Sharma, S., Lin, J., Choi, S. H., Han, H., Yoo, C. B., Egger, G., Yang, A. S., & Jones, P. A. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00484-09 · Cited by 194 · see citing works
Structure and function of the nucleosome-binding PWWP domain
Su, Q., & Min, J. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.09.001 · Cited by 191 · see citing works
Structural and Histone Binding Ability Characterizations of Human PWWP Domains
Wu, H., Zeng, H., Lam, R., Tempel, W., Amaya, M. F., Xu, C., Dombrovski, L., Qiu, W., Wang, Y., & Min, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018919 · Cited by 178 · see citing works
CpGcluster: a distance-based algorithm for CpG-island detection
Hackenberg, M., Previti, C., Luque‐Escamilla, P. L., Carpena, P., Martı́nez-Aroza, J., & Oliver, J. L. T. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-446 · Cited by 178 · see citing works
Jung, H. R., Pasini, D., Helin, K., & Jensen, O. N. (2010) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m900489-mcp200 · Cited by 136 · see citing works
Three novel DNMT3B mutations in Japanese patients with ICF syndrome
Shirohzu, H., Kubota, T., Kumazawa, A., Sado, T., Chijiwa, T., Inagaki, K., Suetake, I., Tajima, S., Wakui, K., Miki, Y., et al. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10658 · Cited by 112 · see citing works
Jin, B., Ernst, J., Tiedemann, R. L., Xu, H., Sureshchandra, S., Kellis, M., Dalton, S., Liu, C., Choi, J.-H., & Robertson, K. D. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.10.017 · Cited by 101 · see citing works
Zhang, Y., Xie, S., Zhou, Y., Xie, Y., Liu, P., Sun, M., Xiao, H., Jin, Y., Sun, X., Zhu, C. H., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.031 · Cited by 81 · see citing works
Nucleosomes protect DNA from DNA methylation in vivo and in vitro
Felle, M., Hoffmeister, H., Rothammer, J., Fuchs, A., Exler, J. H., & Längst, G. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr263 · Cited by 78 · see citing works
Application of histone modification-specific interaction domains as an alternative to antibodiesPreprint
Kungulovski, G., Kycia, I., Tamas, R., Jurkowska, R. Z., Kudithipudi, S., Henry, C., Reinhardt, R., Labhart, P., & Jeltsch, A. (2014) · Genome Research · doi:10.1101/gr.170985.113 · Cited by 68 · see citing works
Nanty, L., Carbajosa, G., Heap, G., Ratnieks, F. L. W., van Heel, D. A., Down, T. A., & Rakyan, V. K. (2011) · Genome Research · doi:10.1101/gr.121640.111 · Cited by 65 · see citing works
Chromatin measurements reveal contributions of synthesis and decay to steady‐state mRNA levels
Tippmann, S. C., Ivánek, R., Gaidatzis, D., Schöler, A., Hoerner, L., van Nimwegen, E., Stadler, P. F., Stadler, M. B., & Schübeler, D. (2012) · Molecular Systems Biology · doi:10.1038/msb.2012.23 · Cited by 50 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The diverse roles of DNA methylation in mammalian development and disease
Greenberg, M., & Bourc’his, D. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0159-6 · Cited by 2,158 · see citing works
The DNA methyltransferase family: a versatile toolkit for epigenetic regulation
Lyko, F. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.80 · Cited by 1,475 · see citing works
DNA methylation aging clocks: challenges and recommendations
Bell, C. G., Lowe, R., Adams, P. D., Baccarelli, A. A., Beck, S., Bell, J. T., Christensen, B. C., Gladyshev, V. N., Heijmans, B. T., Horvath, S., et al. (2019) · Genome Biology · doi:10.1186/s13059-019-1824-y · Cited by 1,025 · see citing works
Navigating the DNA methylation landscape of cancer
Nishiyama, A., & Nakanishi, M. (2021) · Trends in Genetics · doi:10.1016/j.tig.2021.05.002 · Cited by 974 · see citing works
DNA methylation: a historical perspective
Mattei, A. L., Bailly, N., & Meissner, A. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.03.010 · Cited by 876 · see citing works
Intragenic DNA methylation prevents spurious transcription initiation
Neri, F., Rapelli, S., Krepelova, A., Incarnato, D., Parlato, C., Basile, G., Maldotti, M., Anselmi, F., & Oliviero, S. (2017) · Nature · doi:10.1038/nature21373 · Cited by 739 · see citing works
Dynamic DNA methylation: In the right place at the right time
Luo, C., Hajkova, P., & Ecker, J. R. (2018) · Science · doi:10.1126/science.aat6806 · Cited by 668 · see citing works
The Cancer Genome Atlas of renal cell carcinoma: findings and clinical implications
Linehan, W. M., & Ricketts, C. J. (2019) · Nature Reviews Urology · doi:10.1038/s41585-019-0211-5 · Cited by 629 · see citing works
The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape
Weinberg, D. N., Papillon-Cavanagh, S., Chen, H., Yue, Y., Chen, X., Rajagopalan, K. N., Horth, C., McGuire, J. T., Xu, X., Nikbakht, H., et al. (2019) · Nature · doi:10.1038/s41586-019-1534-3 · Cited by 524 · see citing works
Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation
Min, J. L., Hemani, G., Hannon, E., Dekkers, K. F., Castillo-Fernandez, J., Luijk, R., Carnero-Montoro, E., Lawson, D. J., Burrows, K., Suderman, M., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00923-x · Cited by 506 · see citing works
Histone lysine methyltransferases in biology and disease
Husmann, D., & Gozani, O. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0298-7 · Cited by 469 · see citing works
Editing the epigenome: technologies for programmable transcription and epigenetic modulation
Thakore, P. I., Black, J. B., Hilton, I. B., & Gersbach, C. A. (2016) · Nature Methods · doi:10.1038/nmeth.3733 · Cited by 451 · see citing works
Born to run: control of transcription elongation by RNA polymerase II
Chen, F. X., Smith, E. R., & Shilatifard, A. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0010-5 · Cited by 447 · see citing works
Genomic imprinting disorders: lessons on how genome, epigenome and environment interact
Monk, D., Mackay, D., Eggermann, T., Maher, E. R., & Riccio, A. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-018-0092-0 · Cited by 437 · see citing works
The language of chromatin modification in human cancers
Zhao, S., Allis, C. D., & Wang, G. G. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00357-x · Cited by 406 · see citing works
DNA methylation loss in late-replicating domains is linked to mitotic cell division
Zhou, W., Dinh, H. Q., Ramjan, Z., Weisenberger, D. J., Nicolet, C. M., Shen, H., Laird, P. W., & Berman, B. P. (2018) · Nature Genetics · doi:10.1038/s41588-018-0073-4 · Cited by 405 · see citing works
Hodes, G. E., Pfau, M. L., Purushothaman, I., Ahn, H. F., Golden, S. A., Christoffel, D. J., Magida, J., Brancato, A., Takahashi, A., Flanigan, M. E., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.1392-15.2015 · Cited by 395 · see citing works
The DNA methyltransferase DNMT3C protects male germ cells from transposon activity
Barau, J., Teissandier, A., Zamudio, N., Roy, S., Nalesso, V., Hérault, Y., Guillou, F., & Bourc’his, D. (2016) · Science · doi:10.1126/science.aah5143 · Cited by 391 · see citing works
DNA methyltransferases and their roles in tumorigenesis
Zhang, W., & Xu, J. (2017) · Biomarker Research · doi:10.1186/s40364-017-0081-z · Cited by 387 · see citing works
Role of Mammalian DNA Methyltransferases in Development
Chen, Z., & Zhang, Y. (2019) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-103019-102815 · Cited by 377 · see citing works
Epigenetic regulatory functions of DNA modifications: 5-methylcytosine and beyond
Breiling, A., & Lyko, F. (2015) · Epigenetics & Chromatin · doi:10.1186/s13072-015-0016-6 · Cited by 353 · see citing works
Harutyunyan, A. S., Krug, B., Chen, H., Papillon‐Cavanagh, S., Zeinieh, M. P., Jay, N. D., Deshmukh, S., Chen, C. C. L., Belle, J. I., Mikael, L. G., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09140-x · Cited by 348 · see citing works
Plant Transgenerational Epigenetics
Quadrana, L., & Colot, V. (2016) · Annual Review of Genetics · doi:10.1146/annurev-genet-120215-035254 · Cited by 333 · see citing works
Efficient targeted DNA methylation with chimeric dCas9–Dnmt3a–Dnmt3L methyltransferase
Stepper, P., Kungulovski, G., Jurkowska, R. Z., Chandra, T., Krueger, F., Reinhardt, R., Reik, W., Jeltsch, A., & Jurkowski, T. P. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1112 · Cited by 326 · see citing works
Aref‐Eshghi, E., Kerkhof, J., Pedro, V. P., Barat‐Houari, M., Pallarès-Ruiz, N., Andrau, J., Lacombe, D., Van‐Gils, J., Fergelot, P., Dubourg, C., et al. (2020) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2020.01.019 · Cited by 323 · see citing works
Epigenetic inheritance and the missing heritability
Trerotola, M., Relli, V., Simeone, P., & Alberti, S. (2015) · Human Genomics · doi:10.1186/s40246-015-0041-3 · Cited by 318 · see citing works
“Both DNMT3A and DNMT3B localize to methylated, CpG-dense regions and preferentially bind to the bodies of transcribed genes but are excluded from regions of active promoters and enhancers [23].”
BackgroundDNA Methylation Reprogramming during Mammalian Development
Zeng, Y., & Chen, T. (2019) · Genes · doi:10.3390/genes10040257 · Cited by 318 · see citing works
On the origin and evolutionary consequences of gene body DNA methylation
Bewick, A. J., Ji, L., Niederhuth, C. E., Willing, E., Hofmeister, B. T., Shi, X., Wang, L., Lu, Z., Rohr, N. A., Hartwig, B., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1604666113 · Cited by 315 · see citing works
Epigenetics of Modified DNA Bases: 5-Methylcytosine and Beyond
Kumar, S., Chinnusamy, V., & Mohapatra, T. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00640 · Cited by 287 · see citing works
Non-CG Methylation in the Human Genome
He, Y., & Ecker, J. R. (2015) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-090413-025437 · Cited by 263 · see citing works
DNA Methylation: Shared and Divergent Features across Eukaryotes
Schmitz, R. J., Lewis, Z., & Goll, M. G. (2019) · Trends in Genetics · doi:10.1016/j.tig.2019.07.007 · Cited by 262 · see citing works
Impaired H3K36 methylation defines a subset of head and neck squamous cell carcinomas
Papillon‐Cavanagh, S., Lü, C., Gayden, T., Mikael, L. G., Béchet, D., Karamboulas, C., Ailles, L., Karamchandani, J., Marchione, D. M., Garcia, B. A., et al. (2017) · Nature Genetics · doi:10.1038/ng.3757 · Cited by 239 · see citing works
Kinde, B., Gabel, H. W., Gilbert, C. S., Griffith, E. C., & Greenberg, M. E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411269112 · Cited by 236 · see citing works
Inflammation and epigenetic regulation in osteoarthritis
Shen, J., Abu-Amer, Y., O'Keefe, R., & McAlinden, A. (2016) · Connective Tissue Research · doi:10.1080/03008207.2016.1208655 · Cited by 230 · see citing works
The interplay between DNA and histone methylation: molecular mechanisms and disease implications
Li, Y., Chen, X., & Lu, C. (2021) · The EMBO Reports · doi:10.15252/embr.202051803 · Cited by 223 · see citing works
MECP2 disorders: from the clinic to mice and back
Lombardi, L. M., Baker, S. A., & Zoghbi, H. Y. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78167 · Cited by 221 · see citing works
Veselovska, L., Smallwood, S. A., Saadeh, H., Stewart-Morgan, K. R., Krueger, F., Maupetit‐Mehouas, S., Arnaúd, P., Tomizawa, S.-I., Andrews, S., & Kelsey, G. (2015) · Genome biology · doi:10.1186/s13059-015-0769-z · Cited by 219 · see citing works
Insights into epigenetic patterns in mammalian early embryos
Xu, R., Li, C., Liu, X., & Gao, S. (2021) · Protein & Cell · doi:10.1007/s13238-020-00757-z · Cited by 216 · see citing works
DNA Methyltransferases in Cancer: Biology, Paradox, Aberrations, and Targeted Therapy
Zhang, J., Yang, C., Wu, C., Cui, W., & Wang, L. (2020) · Cancers · doi:10.3390/cancers12082123 · Cited by 215 · see citing works
Dynamic epigenomic landscapes during early lineage specification in mouse embryos
Zhang, Y., Xiang, Y., Yin, Q., Du, Z., Xu, P., Wang, Q., Fidalgo, M., Xia, W., Li, Y., Zhao, Z., et al. (2017) · Nature Genetics · doi:10.1038/s41588-017-0003-x · Cited by 210 · see citing works
Dynamic changes in histone modifications precede de novo DNA methylation in oocytesPreprint
Stewart-Morgan, K. R., Veselovska, L., Kim, J., Huang, J., Saadeh, H., Tomizawa, S.-I., Smallwood, S. A., Chen, T., & Kelsey, G. (2015) · Genes & Development · doi:10.1101/gad.271353.115 · Cited by 209 · see citing works
Chromatin regulatory mechanisms and therapeutic opportunities in cancer
Valencia, A. M., & Kadoch, C. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0258-1 · Cited by 205 · see citing works
Acute loss of TET function results in aggressive myeloid cancer in mice
An, J., González‐Avalos, E., Chawla, A., Jeong, M., López-Moyado, I. F., Li, W., Goodell, M. A., Chávez, L., Ko, M., & Rao, A. (2015) · Nature Communications · doi:10.1038/ncomms10071 · Cited by 204 · see citing works
SETD2 Restricts Prostate Cancer Metastasis by Integrating EZH2 and AMPK Signaling Pathways
Yuan, H., Han, Y., Wang, X., Li, N., Liu, Q., Yin, Y., Wang, H., Pan, L., Li, L., Song, K., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.05.022 · Cited by 202 · see citing works
Allosteric control of mammalian DNA methyltransferases – a new regulatory paradigm
Jeltsch, A., & Jurkowska, R. Z. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw723 · Cited by 200 · see citing works
The Roles of Human DNA Methyltransferases and Their Isoforms in Shaping the Epigenome
Gujar, H., Weisenberger, D. J., & Liang, G. (2019) · Genes · doi:10.3390/genes10020172 · Cited by 199 · see citing works
Gao, L., Emperle, M., Guo, Y., Grimm, S. A., Ren, W., Adam, S., Uryu, H., Zhang, Z., Chen, D., Yin, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17109-4 · Cited by 198 · see citing works
TET proteins safeguard bivalent promoters from de novo methylation in human embryonic stem cells
Verma, N., Pan, H., Doré, L. C., Shukla, A., Li, Q. V., Pelham‐Webb, B., Teijeiro, V., Gonzãlez, F., Krivtsov, A. V., Chang, C.-J., et al. (2017) · Nature Genetics · doi:10.1038/s41588-017-0002-y · Cited by 196 · see citing works
DNMT3A in LeukemiaPreprint
Brunetti, L., Gundry, M. C., & Goodell, M. A. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a030320 · Cited by 196 · see citing works
Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis
Rinaldi, L., Datta, D., Serrat, J., Morey, L., Solanas, G., Avgustinova, A., Blanco, E., Pons, J., Matallanas, D., von Kriegsheim, A., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.06.020 · Cited by 194 · see citing works
DNA methylation in the pathogenesis of type 2 diabetes in humans
Davegårdh, C., García-Calzón, S., Bacos, K., & Ling, C. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.01.022 · Cited by 194 · see citing works
Early-Life Gene Expression in Neurons Modulates Lasting Epigenetic States
Stroud, H., Su, S. C., Hrvatin, S., Greben, A. W., Renthal, W. R., Boxer, L. D., Nagy, M. A., Hochbaum, D. R., Kinde, B., Gabel, H. W., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.047 · Cited by 186 · see citing works
Establishment and Functions of DNA Methylation in the Germline
Stewart-Morgan, K. R., Veselovska, L., & Kelsey, G. (2016) · Epigenomics · doi:10.2217/epi-2016-0056 · Cited by 185 · see citing works
Dynamics and Context-Dependent Roles of DNA Methylation
Ambrosi, C. M., Manzo, M., & Baubec, T. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.02.008 · Cited by 184 · see citing works
Self-citationGuo, Y., Zhao, S., & Wang, G. G. (2021) · Trends in Genetics · doi:10.1016/j.tig.2020.12.006 · Cited by 184 · see citing works
Mammalian DNA methyltransferases: new discoveries and open questions
Gowher, H., & Jeltsch, A. (2018) · Biochemical Society Transactions · doi:10.1042/bst20170574 · Cited by 173 · see citing works
Greater Than the Sum of Parts: Complexity of the Dynamic Epigenome
Soshnev, A. A., Josefowicz, S. Z., & Allis, C. D. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.004 · Cited by 172 · see citing works
Ginno, P. A., Gaidatzis, D., Feldmann, A., Hoerner, L., Imanci, D., Burger, L., Zilbermann, F., Peters, A. H. F. M., Edenhofer, F., Smallwood, S. A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16354-x · Cited by 171 · see citing works
Self-citationPutting DNA methylation in context: from genomes to gene expression in plants
Niederhuth, C. E., & Schmitz, R. J. (2016) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2016.08.009 · Cited by 170 · see citing works
Histone Marks in the ‘Driver’s Seat’: Functional Roles in Steering the Transcription Cycle
Gates, L. A., Foulds, C. E., & O’Malley, B. W. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.10.004 · Cited by 169 · see citing works
Epigenetics in Insects: Genome Regulation and the Generation of Phenotypic Diversity
Glastad, K. M., Hunt, B. G., & Goodisman, M. A. D. (2018) · Annual Review of Entomology · doi:10.1146/annurev-ento-011118-111914 · Cited by 169 · see citing works
Epigenetic Alterations in Alzheimer’s Disease
Sanchez-Mut, J. V., & Gräff, J. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00347 · Cited by 168 · see citing works
Metabolic Inputs into the Epigenome
Sharma, U., & Rando, O. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.02.003 · Cited by 167 · see citing works
In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse
Morselli, M., Pastor, W. A., Montanini, B., Nee, K., Ferrari, R., Fu, K., Bonora, G., Rubbi, L., Clark, A. T., Ottonello, S., et al. (2015) · eLife · doi:10.7554/elife.06205 · Cited by 167 · see citing works
Aberrant DNA methylation in melanoma: biomarker and therapeutic opportunities
Micevic, G., Theodosakis, N., & Bosenberg, M. (2017) · Clinical Epigenetics · doi:10.1186/s13148-017-0332-8 · Cited by 167 · see citing works
DNA Methylation Targeting: The DNMT/HMT Crosstalk Challenge
Castillo‐Aguilera, O., Depreux, P., Halby, L., Arimondo, P. B., & Goossens, L. (2017) · Biomolecules · doi:10.3390/biom7010003 · Cited by 166 · see citing works
Jeziorska, D. M., Murray, R. J. S., De Gobbi, M., Gaentzsch, R., Garrick, D., Ayyub, H., Chen, T., Li, E., Telenius, J., Lynch, M., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1703087114 · Cited by 166 · see citing works
Epigenetics in teleost fish: From molecular mechanisms to physiological phenotypes
Best, C., Ikert, H., Kostyniuk, D. J., Craig, P. M., Navarro‐Martín, L., Marandel, L., & Mennigen, J. A. (2018) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2018.01.006 · Cited by 165 · see citing works
Evolution of DNA Methylome Diversity in Eukaryotes
de Mendoza, A., Lister, R., & Bogdanović, O. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.11.003 · Cited by 165 · see citing works
Connolly, R. M., Li, H., Jankowitz, R. C., Zhang, Z., Rudek, M. A., Jeter, S. C., Slater, S. A., Powers, P., Wolff, A. C., Fetting, J. H., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1729 · Cited by 163 · see citing works
Histone H3.3 phosphorylation amplifies stimulation-induced transcription
Armache, A., Yang, S., de Paz, A. M., Robbins, L., Durmaz, C., Cheong, J., Ravishankar, A., Daman, A. W., Ahimovic, D. J., Klevorn, T., et al. (2020) · Nature · doi:10.1038/s41586-020-2533-0 · Cited by 161 · see citing works
Duymich, C. E., Charlet, J., Yang, X., Jones, P. A., & Liang, G. (2016) · Nature Communications · doi:10.1038/ncomms11453 · Cited by 159 · see citing works
DNMT3A and TET1 cooperate to regulate promoter epigenetic landscapes in mouse embryonic stem cells
Gu, T., Lin, X., Cullen, S. M., Luo, M., Jeong, M., Estecio, M. R., Shen, J., Hardikar, S., Sun, D., Su, J., et al. (2018) · Genome biology · doi:10.1186/s13059-018-1464-7 · Cited by 157 · see citing works
Shirane, K., Miura, F., Ito, T., & Lorincz, M. C. (2020) · Nature Genetics · doi:10.1038/s41588-020-0689-z · Cited by 157 · see citing works
The histone H3 variant H3.3 regulates gene body DNA methylation in Arabidopsis thaliana
Wollmann, H., Stroud, H., Yelagandula, R., Tarutani, Y., Jiang, D., Li, J., Jamge, B., Takeuchi, H., Holec, S., Nie, X., et al. (2017) · Genome biology · doi:10.1186/s13059-017-1221-3 · Cited by 156 · see citing works
Choi, J., Lyons, D. B., Kim, M. Y., Moore, J. D., & Zilberman, D. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.10.011 · Cited by 152 · see citing works
Veland, N., Lu, Y., Hardikar, S., Gaddis, S., Zeng, Y., Liu, B., Estecio, M. R., Takata, Y., Lin, K., Tomida, M. W., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky947 · Cited by 149 · see citing works
Generating specificity in genome regulation through transcription factor sensitivity to chromatin
Isbel, L., Grand, R. S., & Schübeler, D. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00512-6 · Cited by 149 · see citing works
Self-citationUnderstanding histone H3 lysine 36 methylation and its deregulation in disease
Li, J., Ahn, J. H., & Wang, G. G. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03144-y · Cited by 146 · see citing works
Gene body methylation in cancer: molecular mechanisms and clinical applications
Wang, Q., Xiong, F., Wu, G., Liu, W., Chen, J., Wang, B., & Chen, Y. (2022) · Clinical Epigenetics · doi:10.1186/s13148-022-01382-9 · Cited by 146 · see citing works
Li, Y., Zheng, H., Wang, Q., Zhou, C., Wei, L., Liu, X., Zhang, W., Zhang, Y., Du, Z., Wang, X., et al. (2018) · Genome biology · doi:10.1186/s13059-018-1390-8 · Cited by 144 · see citing works
A comprehensive epigenome atlas reveals DNA methylation regulating skeletal muscle development
Yang, Y., Fan, X., Yan, J., Chen, M., Zhu, M., Tang, Y., Liu, S., & Tang, Z. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa1203 · Cited by 142 · see citing works
Interplay between chromatin marks in development and disease
Janssen, S. M., & Lorincz, M. C. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-021-00416-x · Cited by 141 · see citing works
TET Enzymes and 5hmC in Adaptive and Innate Immune Systems
Lio, C. J., & Rao, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00210 · Cited by 139 · see citing works
Rondelet, G., Maso, T. D., Willems, L., & Wouters, J. (2016) · Journal of Structural Biology · doi:10.1016/j.jsb.2016.03.013 · Cited by 137 · see citing works
Nashun, B., Hill, P. W. S., Smallwood, S. A., Dharmalingam, G., Amouroux, R., Clark, S. J., Sharma, V., Ndjetehe, E., Pelczar, P., Festenstein, R., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.10.010 · Cited by 133 · see citing works
The roles of histone modifications in tumorigenesis and associated inhibitors in cancer therapy
Yang, Y., Zhang, M., & Wang, Y. (2022) · Journal of the National Cancer Center · doi:10.1016/j.jncc.2022.09.002 · Cited by 133 · see citing works
Poetsch, A. R., Boulton, S. J., & Luscombe, N. M. (2018) · Genome Biology · doi:10.1186/s13059-018-1582-2 · Cited by 132 · see citing works
The emergence of the brain non-CpG methylation system in vertebrates
de Mendoza, A., Poppe, D., Buckberry, S., Pflueger, J., Albertin, C. B., Daish, T., Bertrand, S., de la Calle‐Mustienes, E., Gómez-Skármeta, J. L., Nery, J. R., et al. (2021) · Nature Ecology & Evolution · doi:10.1038/s41559-020-01371-2 · Cited by 130 · see citing works
The role and mechanisms of DNA methylation in the oocyte
Sendžikaitė, G., & Kelsey, G. (2019) · Essays in Biochemistry · doi:10.1042/ebc20190043 · Cited by 129 · see citing works
Epigenetic regulation in development: is the mouse a good model for the human?
Hanna, C. W., Demond, H., & Kelsey, G. (2018) · Human Reproduction Update · doi:10.1093/humupd/dmy021 · Cited by 126 · see citing works
Shaping the cellular landscape with Set2/SETD2 methylation
McDaniel, S. L., & Strahl, B. D. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2517-x · Cited by 125 · see citing works
Paradoxical association of TET loss of function with genome-wide DNA hypomethylation
López-Moyado, I. F., Tsagaratou, A., Yuita, H., Seo, H., Delatte, B., Heinz, S., Benner, C. W., & Rao, A. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1903059116 · Cited by 125 · see citing works
Sharma, G., Upadhyay, S., Srilalitha, M., Nandicoori, V. K., & Khosla, S. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv261 · Cited by 121 · see citing works
B cell activation and plasma cell differentiation are inhibited by de novo DNA methylation
Barwick, B. G., Scharer, C. D., Martinez, R. J., Price, M. J., Wein, A. N., Haines, R. R., Bally, A. P. R., Kohlmeier, J. E., & Boss, J. M. (2018) · Nature Communications · doi:10.1038/s41467-018-04234-4 · Cited by 121 · see citing works
Isoform‐specific localization of DNMT3A regulates DNA methylation fidelity at bivalent CpG islands
Manzo, M., Wirz, J., Ambrosi, C. M., Villaseñor, R., Roschitzki, B., & Baubec, T. (2017) · The EMBO Journal · doi:10.15252/embj.201797038 · Cited by 120 · see citing works
Self-citationPRC2 functions in development and congenital disorders
Deevy, O., & Bracken, A. P. (2019) · Development · doi:10.1242/dev.181354 · Cited by 120 · see citing works
King, A., Huang, K. Y., Rubbi, L., Liu, S., Wang, C., Wang, Y., Pellegrini, M. A., & Fan, G. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.08.083 · Cited by 119 · see citing works
DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes
Lyons, D. B., & Zilberman, D. (2017) · eLife · doi:10.7554/elife.30674 · Cited by 116 · see citing works
DNA methylation dynamics and dysregulation delineated by high-throughput profiling in the mouse
Zhou, W., Hinoue, T., Barnes, B., Mitchell, O. D., Iqbal, W., Lee, S. M., Foy, K. K., Lee, K., Moyer, E. J., VanderArk, A., et al. (2022) · Cell Genomics · doi:10.1016/j.xgen.2022.100144 · Cited by 115 · see citing works
- Authors
- Baubec, T., Colombo, D. F., Wirbelauer, C., Schmidt, J., Burger, L., Krebs, A. R., Akalin, A., & Schübeler, D.
- Affiliations
- Friedrich Miescher Institute (CH)
- University of Basel (CH)
- Corresponding author
- Baubec, Tuncay
- Schübeler, Dirk
- Venue
- Nature
- Published
- 2015-01-21
- Volume
- 520
- Issue
- 7546
- Pages
- 243-247
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2092116145
- Cited by
- 705
- References
- 51
- Citations by year
- 2026: 48 · 2025: 43 · 2024: 48 · 2023: 60 · 2022: 69 · 2021: 53 · 2020: 70 · 2019: 70 · 2018: 66 · 2017: 75 · 2016: 59 · 2015: 42 · 2012: 1
- FWCI
- 34.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- DNMT3A, DNMT3B, de novo methylation, gene body methylation, PWWP domain, H3K36me3, SETD2, histone H3 lysine 36 methylation, mouse embryonic stem cells, chromatin targeting, transcriptional repression, epigenetic regulation
- MeSH terms
- DNA Methyltransferase 3A, DNA Methyltransferase 3B, Animals, Cell Line, Chromatin, DNA (Cytosine-5-)-Methyltransferases, Enhancer Elements, Genetic, Histones, Lysine, Promoter Regions, Genetic, Protein Binding, Histone-Lysine N-Methyltransferase, Transcription, Genetic, Genome, Protein Structure, Tertiary, CpG Islands, DNA Methylation, Protein Transport, Genomics, Epigenesis, Genetic, Mice, Embryonic Stem Cells
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
