Histone demethylase KDM6A directly senses oxygen to control chromatin and cell fate
Open accessAbstract
Oxygen sensing revisited: The cellular response to hypoxia (oxygen deficiency) is a contributing factor in many human diseases. Previous studies examining the way in which hypoxia alters gene expression have focused on oxygen-sensing enzymes that regulate the activity of a transcription factor called hypoxia-inducible factor (see the Perspective by Gallipoli and Huntly). Chakraborty et al. and Batie et al. now show that hypoxia can also affect gene expression through direct effects on chromatin regulators. Certain histone demethylases, such as KDM6A and KDM5A, were found to be direct sensors of oxygen. In cell-culture models, hypoxia diminished the activity of these enzymes and caused changes in the expression of genes that govern cell fate. Science , this issue p. 1217 , p. 1222 ; see also p. 1148
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Hypoxia directly modulates the enzymatic activity of histone demethylases independently of HIF, with implications for cancer metabolism.
“Hypoxia has been found to directly modulate the enzymatic activity of histone demethylases independently of HIF, with important implications for the control of metabolism in cancers.”
From HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells (2021) · cites this paper as [110]
The paper’s Abstract reports that hypoxia promotes histone methylation independently of HIF and identifies KDM6A as an oxygen-sensitive histone demethylase. It also discusses effects on cell differentiation and malignant transformation, including findings in cancer cells and tumors, but does not establish an effect on the control of metabolism in cancers. (LLM, conf=0.88)
Experimental — accuracy not yet measuredRapid histone hypermethylation during hypoxia occurs independently of HIF-1 and of other known hypoxia-inducible inhibitors of KDM activity such as reactive oxygen species and 2-hydroxyglutarate.
“These rapid histone hypermethylations occurred independently of HIF-1 and of other known hypoxia-inducible inhibitors of KDM activity, such as reactive oxygen species and 2-hydroxyglutarate [110,111].”
From HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells (2021) · cites this paper as [110]
The passage labeled Abstract (page unavailable) reports hypoxia-induced histone hypermethylation in cells unable to mount a HIF response. It also concludes that increased 2-hydroxyglutarate and reactive oxygen species did not explain the effect. The passages do not establish the claimed rapid timing. (LLM, conf=0.84)
Experimental — accuracy not yet measuredKDM5A and KDM6A are oxygen sensors that become inactivated during hypoxia, causing rapid histone hypermethylation.
“Two members of the Jumonji domain KDM enzymes, KDM5A and KDM 6A, were recently implicated as oxygen sensors that become inactivated during hypoxia, causing rapid histone hypermethylation [110,111].”
From HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells (2021) · cites this paper as [110]
In the paper’s main text (indexed as Abstract; page unavailable), the authors report low oxygen affinity for KDM5A and KDM6A and hypoxia-induced histone hypermethylation. They identify KDM6A as an oxygen sensor and argue that KDM5A likely plays a similar role. The passages establish the effect but do not establish the claim’s qualifier that hypermethylation occurs rapidly. (LLM, conf=0.84)
Experimental — accuracy not yet measuredHistone demethylases KDM5A and KDM6A sense oxygen concentrations and modulate H3K4me3 and H3K27me3 levels.
“The recent discovery that histone demethylases KDM5A and KDM6A (also known as UTX) can sense oxygen concentrations and thereby modulate H3K4me3 and H3K27me3 levels 91,92 is a first step in this direction.”
From Advances in epigenetics link genetics to the environment and disease (2019) · cites this paper as [92]
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Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400 · see citing works
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
Trapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., & Pachter, L. (2010) · Nature Biotechnology · doi:10.1038/nbt.1621 · Cited by 15,556 · see citing works
Robinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390 · see citing works
Mi, H., Huang, X., Muruganujan, A., Tang, H., Mills, C., Kang, D. S., & Thomas, P. D. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1138 · Cited by 1,985 · see citing works
Expansion of the Gene Ontology knowledgebase and resources
The Gene Ontology Consortium (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw1108 · Cited by 1,850 · see citing works
Oxygen in Stem Cell Biology: A Critical Component of the Stem Cell Niche
Mohyeldin, A., Garzón-Muvdi, T., & Quiñones‐Hinojosa, A. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.07.007 · Cited by 1,535 · see citing works
An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells
Rohle, D., Popovici-Muller, J., Palaskas, N., Turcan, S., Grommes, C., Campos, C., Tsoi, J., Clark, O., Oldrini, B., Komisopoulou, E., et al. (2013) · Science · doi:10.1126/science.1236062 · Cited by 1,153 · see citing works
Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells
Carey, B. W., Finley, L. W. S., Cross, J. R., Allis, C. D., & Thompson, C. B. (2015) · Nature · doi:10.1038/nature13981 · Cited by 1,007 · see citing works
Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition
Higgins, D. F., Kimura, K., Bernhardt, W. M., Shrimanker, N., Akai, Y., Hohenstein, B., Saito, Y., Johnson, R. S., Kretzler, M., Cohen, C. D., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30487 · Cited by 976 · see citing works
A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response
Kruidenier, L., Chung, C.-W., Cheng, Z., Liddle, J., Che, K., Joberty, G., Bantscheff, M., Bountra, C., Bridges, A., Diallo, H., et al. (2012) · Nature · doi:10.1038/nature11262 · Cited by 950 · see citing works
Design and analysis of ChIP-seq experiments for DNA-binding proteins
Kharchenko, P., Tolstorukov, M., & Park, P. J. (2008) · Nature Biotechnology · doi:10.1038/nbt.1508 · Cited by 950 · see citing works
Self-citationCharacterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor
Hirsilä, M., Koivunen, P., Günzler, V., Kivirikko, K. I., & Myllyharju, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304982200 · Cited by 794 · see citing works
Self-citationThe von Hippel–Lindau tumour suppressor protein: O2 sensing and cancer
Kaelin, W. G. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2502 · Cited by 731 · see citing works
Self-citationTransformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation
Koivunen, P., Lee, S., Duncan, C. G., Lopez, G., Lu, G., Ramkissoon, S., Losman, J. A., Joensuu, P., Bergmann, U., Gross, S., et al. (2012) · Nature · doi:10.1038/nature10898 · Cited by 727 · see citing works
Self-citationTumour hypoxia causes DNA hypermethylation by reducing TET activity
Thienpont, B., Steinbacher, J., Zhao, H., D’Anna, F., Kuchnio, A., Ploumakis, A., Ghesquière, B., Van Dyck, L., Boeckx, B., Schoonjans, L., et al. (2016) · Nature · doi:10.1038/nature19081 · Cited by 635 · see citing works
What a difference a hydroxyl makes: mutant IDH, (<i>R</i>)-2-hydroxyglutarate, and cancer
Losman, J.-A., & Kaelin, W. G. (2013) · Genes & Development · doi:10.1101/gad.217406.113 · Cited by 570 · see citing works
Self-citationHypoxia Induces Production of L-2-Hydroxyglutarate
Intlekofer, A. M., Dematteo, R. G., Venneti, S., Finley, L. W. S., Lu, C., Judkins, A. R., Rustenburg, A. S., Grinaway, P. B., Chodera, J. D., Cross, J. R., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.023 · Cited by 513 · see citing works
The UCSC Genome Browser database: 2018 update
Casper, J., Zweig, A. S., Villarreal, C., Tyner, C., Speir, M. L., Rosenbloom, K. R., Raney, B. J., Lee, C. M., Lee, B. T., Karolchik, D., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gkx1020 · Cited by 475 · see citing works
S-2-hydroxyglutarate regulates CD8(+) T-lymphocyte fate
Tyrakis, P. A., Palazon, A., Macias, D., Lee, K. L., Phan, A. T., Veliça, P., You, J., Chia, G. S., Sim, J., Doedens, A., et al. (2016) · Nature · doi:10.1038/nature20165 · Cited by 433 · see citing works
[10] Posttranslational enzymes in the biosynthesis of collagen: Intracellular enzymes
Kivirikko, K. I., & Myllylä, R. (1982) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(82)82067-3 · Cited by 411 · see citing works
Hypoxia induces rapid changes to histone methylation and reprograms chromatin
Batie, M., Frost, J., Frost, M., Wilson, J. W., Schofield, P., & Rocha, S. (2019) · Science · doi:10.1126/science.aau5870 · Cited by 385 · see citing works
Oldham, W. M., Clish, C. B., Yang, Y., & Loscalzo, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.021 · Cited by 364 · see citing works
Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system
Cho, S. H., Raybuck, A. L., Stengel, K. R., Wei, M., Beck, T. C., Volanakis, E. J., Thomas, J. W., Hiebert, S. W., Haase, V. H., & Boothby, M. R. (2016) · Nature · doi:10.1038/nature19334 · Cited by 307 · see citing works
Safran, M., Kim, W. Y., O'Connell, F., Flippin, L., Günzler, V., Horner, J. W., DePinho, R. A., & Kaelin, W. G. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509459103 · Cited by 305 · see citing works
Self-citationStructural studies on human 2-oxoglutarate dependent oxygenases
McDonough, M. A., Loenarz, C., Chowdhury, R., Clifton, I. J., & Schofield, C. J. (2010) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2010.08.006 · Cited by 280 · see citing works
Watson, C. J., Collier, P. H., Tea, I., Neary, R., Watson, J. A., Robinson, C. M., Phelan, D. M. J., Ledwidge, M. T., McDonald, K., McCann, A. H., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt614 · Cited by 278 · see citing works
L-2-Hydroxyglutarate production arises from noncanonical enzyme function at acidic pH
Intlekofer, A. M., Wang, B., Liu, H., Shah, H., Carmona-Fontaine, C., Rustenburg, A. S., Salah, S., Gunner, M. R., Chodera, J. D., Cross, J. R., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2307 · Cited by 268 · see citing works
PRC2 mediated H3K27 methylations in cellular identity and cancer
Conway, E., Healy, E., & Bracken, A. P. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2015.10.003 · Cited by 239 · see citing works
UTX mediates demethylation of H3K27me3 at muscle‐specific genes during myogenesis
Seenundun, S., Rampalli, S., Liu, Q., Aziz, A., Palii, C. G., Hong, S., Blais, A., Brand, M., Ge, K., & Dilworth, F. J. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.37 · Cited by 235 · see citing works
Failure to prolyl hydroxylate hypoxia‐inducible factor α phenocopies VHL inactivation in vivo
Kim, W. Y., Safran, M., Buckley, M. R., Ebert, B. L., Glickman, J., Bosenberg, M., Regan, M., & Kaelin, W. G. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601300 · Cited by 235 · see citing works
Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER
van den Beucken, T., Koch, E., Chu, K., Rupaimoole, R., Prickaerts, P., Adriaens, M. E., Voncken, J. W., Harris, A. L., Buffa, F. M., Haider, S. A., et al. (2014) · Nature Communications · doi:10.1038/ncomms6203 · Cited by 226 · see citing works
Ler, L. D., Ghosh, S., Chai, X., Thike, A. A., Heng, H. L., Siew, E. Y., Dey, S., Koh, L. K., Lim, J. Q., Lim, W. K., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aai8312 · Cited by 208 · see citing works
Cornwell, M., Vangala, M., Taing, L., Herbert, Z. T., Köster, J., Li, B., Sun, H., Li, T., Zhang, J., Qiu, X., et al. (2018) · BMC Bioinformatics · doi:10.1186/s12859-018-2139-9 · Cited by 203 · see citing works
Self-citationWakimoto, H., Tanaka, S., Curry, W. T., Loebel, F., Zhao, D., Tateishi, K., Chen, J., Klofas, L. K., Lelic, N., Kim, J. C., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-3052 · Cited by 190 · see citing works
FirebrowseR: an R client to the Broad Institute’s Firehose Pipeline
Deng, M., Brägelmann, J., Kryukov, I. L., et al. (2016) · Database · doi:10.1093/database/baw160 · Cited by 187 · see citing works
ROS: Really involved in Oxygen Sensing
Kaelin, W. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.006 · Cited by 173 · see citing works
Self-citationTET1-Mediated Hydroxymethylation Facilitates Hypoxic Gene Induction in Neuroblastoma
Mariani, C. J., Vasanthakumar, A., Madžo, J., Yesilkanal, A. E., Bhagat, T. D., Yu, Y., Bhattacharyya, S., Wenger, R. H., Cohn, S. L., Nanduri, J., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.04.040 · Cited by 165 · see citing works
Structural basis for histone H3 Lys 27 demethylation by UTX/KDM6APreprint
Sengoku, T., & Yokoyama, S. (2011) · Genes & Development · doi:10.1101/gad.172296.111 · Cited by 162 · see citing works
Epigenetic Regulation by Histone Demethylases in Hypoxia
Hancock, R. L., Dunne, K., Walport, L. J., Flashman, E., & Kawamura, A. (2015) · Epigenomics · doi:10.2217/epi.15.24 · Cited by 162 · see citing works
Adaptive Myogenesis under Hypoxia
Yun, Z., Lin, Q., & Giaccia, A. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.8.3040-3055.2005 · Cited by 145 · see citing works
Chromatin as an oxygen sensor and active player in the hypoxia response
Melvin, A., & Rocha, S. (2011) · Cellular Signalling · doi:10.1016/j.cellsig.2011.08.019 · Cited by 121 · see citing works
ChiLin: a comprehensive ChIP-seq and DNase-seq quality control and analysis pipeline
Qin, Q., Mei, S., Wu, Q., Sun, H., Li, L., Taing, L., Chen, S., Li, F., Liu, T., Zang, C., et al. (2016) · BMC Bioinformatics · doi:10.1186/s12859-016-1274-4 · Cited by 119 · see citing works
Histone H3 Lysine 27 demethylases Jmjd3 and Utx are required for T-cell differentiation
Manna, S., Kim, J. K., Baugé, C., Cam, M. C., Zhao, Y., Shetty, J., Vacchio, M. S., Castro, E., Tran, B. Q., Tessarollo, L., et al. (2015) · Nature Communications · doi:10.1038/ncomms9152 · Cited by 113 · see citing works
Chromatin and oxygen sensing in the context of JmjC histone demethylases
Shmakova, A., Batie, M., Druker, J., & Rocha, S. (2014) · Biochemical Journal · doi:10.1042/bj20140754 · Cited by 99 · see citing works
Hypoxia in the thymus: role of oxygen tension in thymocyte survival
Hale, L. P., Braun, R. D., Gwinn, W. M., Greer, P. K., & Dewhirst, M. W. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00682.2001 · Cited by 87 · see citing works
Hypoxia increases genome-wide bivalent epigenetic marking by specific gain of H3K27me3
Prickaerts, P., Adriaens, M. E., van den Beucken, T., Koch, E., Dubois, L. J., Dahlmans, V. E. H., Gits, C. M. M., Evelo, C. T., Chan‐Seng‐Yue, M., Wouters, B. G., et al. (2016) · Epigenetics & Chromatin · doi:10.1186/s13072-016-0086-0 · Cited by 87 · see citing works
Váraljai, R., Islam, A. B. M. M. K., Beshiri, M. L., Rehman, J., López-Bigas, N., & Benevolenskaya, E. V. (2015) · Genes & Development · doi:10.1101/gad.264036.115 · Cited by 82 · see citing works
Majmundar, A. J., Skuli, N., Mesquita, R. C., Kim, M. N., Yodh, A. G., Nguyen-McCarty, M., & Simon, M. C. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05857-11 · Cited by 75 · see citing works
Learning To Breathe: Developmental Phase Transitions in Oxygen Status
Considine, M. J., Díaz‐Vivancos, P., Kerchev, P., et al. (2016) · Trends in Plant Science · doi:10.1016/j.tplants.2016.11.013 · Cited by 75 · see citing works
Numayama‐Tsuruta, K., Kobayashi, A., Sogawa, K., & Fujii‐Kuriyama, Y. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.00486.x · Cited by 66 · see citing works
Laukka, T., Myllykoski, M., Looper, R., & Koivunen, P. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.06.048 · Cited by 65 · see citing works
Self-citationCreech, A. L., Taylor, J. E., Maier, V., Wu, X., Feeney, C. M., Udeshi, N. D., Peach, S. E., Boehm, J. S., Lee, J. T., Carr, S. A., et al. (2014) · Methods · doi:10.1016/j.ymeth.2014.10.033 · Cited by 62 · see citing works
Self-citationAdriaens, M. E., Prickaerts, P., Chan‐Seng‐Yue, M., van den Beucken, T., Dahlmans, V. E. H., Eijssen, L., Beck, T., Wouters, B. G., Voncken, J. W., & Evelo, C. T. (2016) · Epigenetics & Chromatin · doi:10.1186/s13072-016-0090-4 · Cited by 27 · see citing works
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- Authors
- Chakraborty, A. A., Laukka, T., Myllykoski, M., Ringel, A. E., Booker, M. A., Tolstorukov, M. Y., Meng, Y. J., Meier, S. R., Jennings, R. B., Creech, A. L., Herbert, Z. T., McBrayer, S. K., Olenchock, B. A., Jaffe, J. D., Haigis, M. C., Beroukhim, R., Signoretti, S., Koivunen, P., & Kaelin, W. G.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Oulu (FI)
- Harvard University (US)
- Broad Institute (US)
- Corresponding author
- Koivunen, Peppi
- Kaelin, William G.
- ORCID
- Chakraborty, Abhishek A.
- Laukka, Tuomas
- Myllykoski, Matti
- Ringel, Alison E.
- Booker, Matthew A.
- Tolstorukov, Michael Y.
- Meng, Yuzhong Jeff
- Meier, Samuel R.
- Jennings, Rebecca B.
- Creech, Amanda L.
- Herbert, Zachary T.
- McBrayer, Samuel K.
- Olenchock, Benjamin A.
- Jaffe, Jacob D.
- Haigis, Marcia C.
- Beroukhim, Rameen
- Signoretti, Sabina
- Koivunen, Peppi
- Kaelin, William G.
- Venue
- Science
- Published
- 2019-03-15
- Volume
- 363
- Issue
- 6432
- Pages
- 1217-1222
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7336390
- OpenAlex
- W2922176925
- Cited by
- 432
- References
- 55
- Citations by year
- 2026: 39 · 2025: 53 · 2024: 56 · 2023: 60 · 2022: 60 · 2021: 64 · 2020: 66 · 2019: 33 · 2018: 1
- FWCI
- 18.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R35CA210068, P50CA101942, R01CA068490, T32CA009361)
- Academy of Finland (266719, 308009)
- S. Juselius Foundation
- Jane and Aatos Erkko Foundation
- American Cancer Society (PF-14-144-01-TBE)
- Howard Hughes Medical Institute
- 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 › Molecular Biology › Cancer-related gene regulation
- Keywords
- KDM6A, oxygen sensing, hypoxia, 2-oxoglutarate-dependent dioxygenase, histone demethylase, H3K27 demethylation, histone methylation, chromatin regulation, cell fate, cell differentiation, 2-hydroxyglutarate, KDM6B
- MeSH terms
- Animals, Chromatin, Histones, Humans, Methylation, Nuclear Proteins, Oxygen, Cell Hypoxia, Mice, Hypoxia-Inducible Factor 1, Histone Demethylases, Jumonji Domain-Containing Histone Demethylases, HEK293 Cells, MCF-7 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 ›
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