An Enhancer Element Harboring Variants Associated with Systemic Lupus Erythematosus Engages the TNFAIP3 Promoter to Influence A20 Expression
Open accessAbstract
Functional characterization of causal variants present on risk haplotypes identified through genome-wide association studies (GWAS) is a primary objective of human genetics. In this report, we evaluate the function of a pair of tandem polymorphic dinucleotides, 42 kb downstream of the promoter of TNFAIP3, (rs148314165, rs200820567, collectively referred to as TT>A) recently nominated as causal variants responsible for genetic association of systemic lupus erythematosus (SLE) with tumor necrosis factor alpha inducible protein 3 (TNFAIP3). TNFAIP3 encodes the ubiquitin-editing enzyme, A20, a key negative regulator of NF-κB signaling. A20 expression is reduced in subjects carrying the TT>A risk alleles; however, the underlying functional mechanism by which this occurs is unclear. We used a combination of electrophoretic mobility shift assays (EMSA), mass spectrometry (MS), reporter assays, chromatin immunoprecipitation-PCR (ChIP-PCR) and chromosome conformation capture (3C) EBV transformed lymphoblastoid cell lines (LCL) from individuals carrying risk and non-risk TNFAIP3 haplotypes to characterize the effect of TT>A on A20 expression. Our results demonstrate that the TT>A variants reside in an enhancer element that binds NF-κB and SATB1 enabling physical interaction of the enhancer with the TNFAIP3 promoter through long-range DNA looping. Impaired binding of NF-κB to the TT>A risk alleles or knockdown of SATB1 expression by shRNA, inhibits the looping interaction resulting in reduced A20 expression. Together, these data reveal a novel mechanism of TNFAIP3 transcriptional regulation and establish the functional basis by which the TT>A risk variants attenuate A20 expression through inefficient delivery of NF-κB to the TNFAIP3 promoter. These results provide critical functional evidence supporting a direct causal role for TT>A in the genetic predisposition to SLE.
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A systemic lupus erythematosus-associated variant (TT > A) situated within an enhancer downstream of TNFAIP3 abrogates NF-kB binding, affecting TNFAIP3 expression.
“In another example, a systemic lupus erythematosus-associated variant (termed TT > A) situated within an enhancer downstream of TNFAIP3 has been shown to abrogate NF-kB binding, affecting TNFAIP3 expression [211, 212].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [212]
The Abstract identifies TT>A as an SLE-associated variant in a downstream enhancer and reports reduced A20 expression, the protein encoded by TNFAIP3. The Results section, “The TT>A risk alleles bind NF-κB subunits with reduced affinity” (page unavailable), finds impaired NF-κB binding—not that binding is abrogated. The claim overstates that effect. (LLM, conf=0.90)
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Cites
Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease
The International IBD Genetics Consortium (IIBDGC), Jostins, L., Ripke, S., Weersma, R. K., Duerr, R. H., McGovern, D. P., Hui, K. Y., Lee, J. C., Philip Schumm, L., Sharma, Y., et al. (2012) · Nature · doi:10.1038/nature11582 · Cited by 4,722 · see citing works
Hindorff, L. A., Sethupathy, P., Junkins, H. A., Ramos, E. M., Mehta, J. P., Collins, F. S., & Manolio, T. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903103106 · Cited by 4,013 · see citing works
Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathways
Nair, R. P., Duffin, K. C., Helms, C. A., Ding, J., Stuart, P. E., Goldgar, D. E., Gudjonsson, J. E., Li, Y., Tejasvi, T., Feng, B., et al. (2009) · Nature Genetics · doi:10.1038/ng.311 · Cited by 1,414 · see citing works
Failure to Regulate TNF-Induced NF-κB and Cell Death Responses in A20-Deficient Mice
Lee, E. G., Boone, D. L., Chai, S., Libby, S. L., Chien, M., Lodolce, J. P., & Ma, A. (2000) · Science · doi:10.1126/science.289.5488.2350 · Cited by 1,409 · see citing works
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci
BIRAC Consortium, Stahl, E. A., YEAR Consortium, Raychaudhuri, S., Remmers, E. F., Xie, G., Eyre, S., Thomson, B. P., Li, Y., Kurreeman, F. A. S., et al. (2010) · Nature Genetics · doi:10.1038/ng.582 · Cited by 1,253 · see citing works
Mutations of multiple genes cause deregulation of NF-kB in diffuse large B-cell lymphoma
Compagno, M., Lim, W., Grunn, A., Nandula, S., Brahmachary, M., Shen, Q., Bertoni, F., Ponzoni, M., Scandurra, M., Califano, A., et al. (2009) · Nature · doi:10.1038/nature07968 · Cited by 1,116 · see citing works
The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses
Boone, D. L., Turer, E. E., Lee, E. G., Ahmad, R., Wheeler, M. T., Tsui, C., Hurley, P. J., Chien, M., Chai, S., Hitotsumatsu, O., et al. (2004) · Nature Immunology · doi:10.1038/ni1110 · Cited by 1,091 · see citing works
Strange, A., Spencer, C. C. A., Band, G., Bellenguez, C., Freeman, C., Pirinen, M., Rautanen, A., Su, Z., Donnelly, P., Capon, F., et al. (2010) · Nature Genetics · doi:10.1038/ng.694 · Cited by 1,042 · see citing works
Multiple common variants for celiac disease influencing immune gene expression
Dubois, P. C. A., Trynka, G., Franke, L., Hunt, K. A., Romanos, J., Curtotti, A., Zhernakova, A., Heap, G., Ádány, R., Aromaa, A. J., et al. (2010) · Nature Genetics · doi:10.1038/ng.543 · Cited by 1,026 · see citing works
Han, J., Zheng, H., Cui, Y., Sun, L., Ye, D., Hu, Z. Q., Xu, J., Cai, Z., Huang, W., Zhao, G., et al. (2009) · Nature Genetics · doi:10.1038/ng.472 · Cited by 938 · see citing works
Quantitative analysis of chromosome conformation capture assays (3C-qPCR)
Hagège, H., Klous, P., Braem, C., Splinter, E., Dekker, J., Cathala, G., de Laat, W., & Forné, T. (2007) · Nature Protocols · doi:10.1038/nprot.2007.243 · Cited by 720 · cited 1× · see citing works
“3C-qPCR assay We performed the 3C-qPCR assays as described [40] with minor modifications.”
MethodGenetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus
Graham, R., Cotsapas, C. J., Davies, L. R. L., Hackett, R., Lessard, C. J., Leon, J. M., Burtt, N. P., Guiducci, C., Parkin, M., Gates, C., et al. (2008) · Nature Genetics · doi:10.1038/ng.200 · Cited by 588 · see citing works
Self-citationFrequent inactivation of A20 in B-cell lymphomas
Kato, M., Sanada, M., Kato, I., Sato, Y., Takita, J., Takeuchi, K., Niwa, A., Chen, Y., Nakazaki, K., Nomoto, J., et al. (2009) · Nature · doi:10.1038/nature07969 · Cited by 553 · see citing works
Two independent alleles at 6q23 associated with risk of rheumatoid arthritis
Plenge, R. M., Cotsapas, C. J., Davies, L. R. L., Price, A. L., de Bakker, P. I. W., Maller, J., Pe’er, I., Burtt, N. P., Blumenstiel, B. S., DeFelice, M., et al. (2007) · Nature Genetics · doi:10.1038/ng.2007.27 · Cited by 550 · see citing works
Cai, S., Lee, C. C., & Kohwi-shigematsu, T. (2006) · Nature Genetics · doi:10.1038/ng1913 · Cited by 547 · see citing works
TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma
Schmitz, R., Hansmann, M., Bohle, V., Martín-Subero, J. I., Hartmann, S., Mechtersheimer, G., Klapper, W., Vater, I., Giefing, M., Gesk, S., et al. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090528 · Cited by 480 · see citing works
Musone, S. L., Taylor, K. E., Lu, T. T., Nititham, J., Ferreira, R. C., Ortmann, W. A., Shifrin, N. T., Petri, M., Kamboh, M. I., Manzi, S., et al. (2008) · Nature Genetics · doi:10.1038/ng.202 · Cited by 470 · see citing works
Rheumatoid arthritis association at 6q23
Thomson, W., Barton, A. C., Ke, X., Eyre, S., Hinks, A., Bowes, J., Donn, R. P., Symmons, D. P. M., Hider, S., Bruce, I. N., et al. (2007) · Nature Genetics · doi:10.1038/ng.2007.32 · Cited by 381 · see citing works
Hitotsumatsu, O., Ahmad, R., Tavares, R. M., Wang, M., Philpott, D. J., Turer, E. E., Lee, B. L., Shiffin, N., Advincula, R., Malynn, B. A., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.02.002 · Cited by 349 · see citing works
The three 'C' s of chromosome conformation capture: controls, controls, controls
Dekker, J. (2005) · Nature Methods · doi:10.1038/nmeth823 · Cited by 347 · see citing works
TNFAIP3/A20 functions as a novel tumor suppressor gene in several subtypes of non-Hodgkin lymphomas
Honma, K., Tsuzuki, S., Nakagawa, M., Tagawa, H., Nakamura, S., Morishima, Y., & Seto, M. (2009) · Blood · doi:10.1182/blood-2008-12-194852 · Cited by 305 · see citing works
Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus
Adrianto, I., Wen, F., Templeton, A., Wiley, G., King, J. B., Lessard, C. J., Bates, J. S., Hu, Y., Kelly, J. A., Kaufman, K. M., et al. (2011) · Nature Genetics · doi:10.1038/ng.766 · Cited by 279 · see citing works
Self-citationThe Ubiquitin Modifying Enzyme A20 Restricts B Cell Survival and Prevents Autoimmunity
Tavares, R. M., Turer, E. E., Liu, C. L., Advincula, R., Scapini, P., Rhee, L., Barrera, J., Lowell, C. A., Utz, P. J., Malynn, B. A., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.07.017 · Cited by 271 · see citing works
A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility
Kochi, Y., Okada, Y., Suzuki, A., Ikari, K., Terao, C. C., Takahashi, A., Yamazaki, K., Hosono, N., Myouzen, K., Tsunoda, T., et al. (2010) · Nature Genetics · doi:10.1038/ng.583 · Cited by 264 · see citing works
Hammer, G. E., Turer, E. E., Taylor, K. E., Fang, C. J., Advincula, R., Oshima, S., Barrera, J., Huang, E. J., Hou, B., Malynn, B. A., et al. (2011) · Nature Immunology · doi:10.1038/ni.2135 · Cited by 243 · see citing works
A20 zinc finger protein inhibits TNF and IL-1 signaling
Jäättelä, M., Mouritzen, H., Elling, F., & Bastholm, L. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.156.3.1166 · Cited by 242 · see citing works
Siggers, T., Chang, A. B., Teixeira, A. S., Wong, D., Williams, K. J., Ahmed, B., Ragoussis, J., Udalova, I. A., Smale, S. T., & Bulyk, M. L. (2011) · Nature Immunology · doi:10.1038/ni.2151 · Cited by 221 · see citing works
Yang, W., Tang, H., Zhang, Y., Tang, X., Zhang, J., Sun, L., Yang, J., Cui, Y., Zhang, L., Hirankarn, N., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.11.018 · Cited by 221 · see citing works
Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-κB signalling
Trynka, G., Zhernakova, A., Romanos, J., Franke, L., Hunt, K. A., Turner, G., Bruinenberg, M., Heap, G., Platteel, M., Ryan, A. W., et al. (2009) · Gut · doi:10.1136/gut.2008.169052 · Cited by 196 · see citing works
Chu, Y., Vahl, J. C., Kumar, D., Heger, K., Bertossi, A., Wojtowicz, E. E., Soberon, V., Schenten, D., Mack, B., Reutelshöfer, M., et al. (2010) · Blood · doi:10.1182/blood-2010-09-306019 · Cited by 191 · see citing works
The genetics of lupus: a functional perspective
Guerra, S. G., Vyse, T. J., & Graham, D. S. C. (2012) · Arthritis Research & Therapy · doi:10.1186/ar3844 · Cited by 150 · see citing works
Dieudé, P., Guedj, M., Wipff, J., Ruiz, B., Riemekasten, G., Matucci‐Cerinic, M., Melchers, I., HACHULLA, E., Airo, P., Diot, É., et al. (2010) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2009.127928 · Cited by 136 · see citing works
A20 is targeted by promoter methylation, deletion and inactivating mutation in MALT lymphoma
Chanudet, E., Huang, Y., Ichimura, K., Dong, G., Hamoudi, R., Radford, J. A., Wotherspoon, A. C., Isaacson, P. G., Ferry, J. A., & Du, M. (2009) · Leukemia · doi:10.1038/leu.2009.234 · Cited by 117 · see citing works
Sequencing of TNFAIP3 and association of variants with multiple autoimmune diseases
Musone, S. L., Taylor, K. E., Nititham, J., Chu, C., Poon, A. W., Liao, W. J., Lam, E. T., Ma, A. I., Kwok, P., & Criswell, L. A. (2011) · Genes and Immunity · doi:10.1038/gene.2010.64 · Cited by 114 · see citing works
Hövelmeyer, N., Reißig, S., Xuân, N. T., Adams‐Quack, P., Lukas, D., Nikolaev, A., Schlüter, D., & Waisman, A. (2010) · European Journal of Immunology · doi:10.1002/eji.201041313 · Cited by 109 · see citing works
Shimane, K., Kochi, Y., Horita, T., Ikari, K., Amano, H., Hirakata, M., Okamoto, A., Yamada, R., Myouzen, K., Suzuki, A., et al. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27190 · Cited by 90 · see citing works
Vaughn, S. E., Kottyan, L. C., Munroe, M. E., & Harley, J. B. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0212095 · Cited by 72 · see citing works
Koumakis, E., Giraud, M., Dieudé, P., Cohignac, V., Cuomo, G., Airò, P., HACHULLA, E., Matucci‐Cerinic, M., Diot, E., Caramaschi, P., et al. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34490 · Cited by 70 · see citing works
SATB1-mediated functional packaging of chromatin into loops
Kohwi-shigematsu, T., Kohwi, Y., Takahashi, K., Richards, H. W., Ayers, S. D., Han, H., & Cai, S. (2012) · Methods · doi:10.1016/j.ymeth.2012.06.019 · Cited by 50 · see citing works
Ainbinder, E., Amir-Zilberstein, L., Yamaguchi, Y., Handa, H., & Dikstein, R. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.6.2444-2454.2004 · Cited by 45 · see citing works
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- [37]Nair RP, Duffin KC, Helms C, Ding J, Stuart PE, et al (2009) Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet 41: 199– 204. 19169254 PMC2745122
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Tsokos, G. C. (2020) · Nature Immunology · doi:10.1038/s41590-020-0677-6 · Cited by 589 · see citing works
Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis
Mohan, C., & Putterman, C. (2015) · Nature Reviews Nephrology · doi:10.1038/nrneph.2015.33 · Cited by 376 · see citing works
Enhancer variants: evaluating functions in common disease
Corradin, O., & Scacheri, P. C. (2014) · Genome Medicine · doi:10.1186/s13073-014-0085-3 · Cited by 241 · see citing works
Immunogenetics of systemic lupus erythematosus: A comprehensive review
Ghodke‐Puranik, Y., & Niewold, T. B. (2015) · Journal of Autoimmunity · doi:10.1016/j.jaut.2015.08.004 · Cited by 223 · see citing works
A20 at the Crossroads of Cell Death, Inflammation, and AutoimmunityPreprint
Martens, A., & Loo, G. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a036418 · Cited by 138 · see citing works
Khatri, B., Tessneer, K. L., Rasmussen, A., Aghakhanian, F. F., Reksten, T. R., Adler, A., Alevizos, I., Anaya, J., Aqrawi, L. A., Baecklund, E., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30773-y · Cited by 120 · see citing works
Self-citationAdvances in lupus genetics and epigenetics
Deng, Y., & Tsao, B. P. (2014) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000086 · Cited by 119 · see citing works
Grimbacher, B., Warnatz, K., Yong, P. F. K., Korganow, A., & Peter, H. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.11.004 · Cited by 115 · see citing works
Deng, Y., & Tsao, B. P. (2017) · Current Rheumatology Reports · doi:10.1007/s11926-017-0695-z · Cited by 113 · see citing works
Common genetic factors among autoimmune diseases
Harroud, A., & Hafler, D. A. (2023) · Science · doi:10.1126/science.adg2992 · Cited by 110 · see citing works
Decoding the genetic and epigenetic basis of asthma
Stikker, B., Hendriks, R. W., & Stadhouders, R. (2023) · Allergy · doi:10.1111/all.15666 · Cited by 95 · see citing works
Identification of atrial fibrillation associated genes and functional non-coding variants
van Ouwerkerk, A. F., Bosada, F. M., van Duijvenboden, K., Hill, M. C., Montefiori, L. E., Scholman, K. T., Liu, J., de Vries, A. A. F., Boukens, B. J., Ellinor, P. T., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12721-5 · Cited by 94 · see citing works
McGovern, A., Schoenfelder, S., Martin, P., Massey, J., Duffus, K., Plant, D., Yarwood, A., Pratt, A. G., Anderson, A. E., Isaacs, J. D., et al. (2016) · Genome biology · doi:10.1186/s13059-016-1078-x · Cited by 91 · see citing works
Clinical reviews in allergy and immunology
Leung, D. Y. M., Ledford, D. K., Wechsler, M. E., Fulkerson, P. C., Bochner, B. S., Gauvreau, G. M., Gleich, G. J., Henkel, T., Kolbeck, R., Mathur, S. K., et al. (2012) · Cited by 87 · see citing works
Systemic lupus erythematosus and immunodeficiency
Sawada, T., Fujimori, D., & Yamamoto, Y. (2019) · Immunological Medicine · doi:10.1080/25785826.2019.1628466 · Cited by 85 · see citing works
Transcriptional enhancers and their communication with gene promoters
Ray-Jones, H., & Spivakov, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03903-w · Cited by 81 · see citing works
A20: A multifunctional tool for regulating immunity and preventing disease
Malynn, B. A., & Ma, A. I. (2019) · Cellular Immunology · doi:10.1016/j.cellimm.2019.04.002 · Cited by 80 · see citing works
Alsheikh, A. J., Wollenhaupt, S., King, E. A., Reeb, J., Ghosh, S., Stolzenburg, L. R., Tamim, S., Lazar, J., Davis, J. W., & Jacob, H. J. (2022) · BMC Medical Genomics · doi:10.1186/s12920-022-01216-w · Cited by 80 · see citing works
Martens, A., Priem, D., Hoste, E., Vetters, J., Rennen, S., Catrysse, L., Voet, S., Deelen, L., Sze, M., Vikkula, H., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0621-9 · Cited by 80 · see citing works
Altonsy, M. O., Sasse, S. K., Phang, T. L., & Gerber, A. N. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.545178 · Cited by 76 · see citing works
Ray, J. P., de Boer, C. G., Fulco, C. P., Lareau, C., Kanai, M., Ulirsch, J., Tewhey, R., Ludwig, L. S., Reilly, S., Bergman, D. T., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15022-4 · Cited by 57 · see citing works
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Ray-Jones, H. F., Eyre, S., Barton, A. C., & Warren, R. B. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2015.11.025 · Cited by 73 · see citing works
Zilberman‐Rudenko, J., Shawver, L., Wessel, A. W., Luo, Y., Pelletier, M., Tsai, W. L., Lee, Y., Vonortas, S., Cheng, L. E., Ashwell, J. D., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1518163113 · Cited by 73 · see citing works
Lareau, C. A., & Aryee, M. J. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btx623 · Cited by 72 · see citing works
A catalog of GWAS fine-mapping efforts in autoimmune disease
Çalışkan, M., Brown, C. D., & Maranville, J. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.03.009 · Cited by 67 · see citing works
A20 and ABIN-1 synergistically preserve intestinal epithelial cell survival
Kattah, M. G., Shao, L., Rosli, Y. Y., Shimizu, H., Whang, M. I., Advincula, R., Achacoso, P., Shah, S. B., Duong, B. H., Onizawa, M., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20180198 · Cited by 59 · see citing works
Modeling genomic regulatory networks with big data
Bolouri, H. (2014) · Trends in Genetics · doi:10.1016/j.tig.2014.02.005 · Cited by 57 · see citing works
Three-dimensional genome organization in immune cell fate and function
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ZHANG, Y. H., Yan, H. Q., Wang, F., WANG, Y. Y., Jiang, Y., Wang, Y. N., & GAO, F. G. (2014) · International Journal of Oncology · doi:10.3892/ijo.2014.2725 · Cited by 55 · see citing works
Niewold, T. B. (2015) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000205 · Cited by 55 · see citing works
Liu, J., Zhu, L., Xie, G.-L., Bao, J.-F., & Yu, Q. (2015) · PLoS ONE · doi:10.1371/journal.pone.0121256 · Cited by 53 · see citing works
Genetics of systemic lupus erythematosus: immune responses and end organ resistance to damage
Dai, C., Deng, Y., Quinlan, A. R., Gaskin, F., Tsao, B. P., & Fu, S. M. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.10.004 · Cited by 50 · see citing works
Roles of A20 in autoimmune diseases
Zhang, M., Peng, L., Wang, Y., Wang, J., Liu, J., Liu, M., Hu, J., Song, B., & Yang, H. (2015) · Immunologic Research · doi:10.1007/s12026-015-8677-6 · Cited by 50 · see citing works
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Liu, X., Tang, A.-L., Chen, J., Gao, N., Zhang, G., & Xiao, C. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1114103 · Cited by 47 · see citing works
Wang, S., Wen, F., Tessneer, K. L., & Gaffney, P. M. (2016) · Genes and Immunity · doi:10.1038/gene.2016.4 · Cited by 41 · see citing works
Self-citationPost-translational control of NF-κB signaling by ubiquitination
Won, M., Byun, H. S., Park, K. A., & Hur, G. M. (2016) · Archives of Pharmacal Research · doi:10.1007/s12272-016-0772-2 · Cited by 41 · see citing works
The genetics revolution in rheumatology: large scale genomic arrays and genetic mapping
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Zhao, H., Wang, L., Luo, H., Li, Q., & Zuo, X. (2017) · Rheumatology · doi:10.1093/rheumatology/kew508 · Cited by 40 · see citing works
The role of 3D genome organization in disease: From compartments to single nucleotides
Chakraborty, A., & Ay, F. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.07.005 · Cited by 39 · see citing works
He, J., Zhang, Q., Zhang, W., Chen, F., Zhao, T., Lin, Y., Li, J., Liu, Y., Liu, Y., & Shao, Y. (2018) · Critical Care · doi:10.1186/s13054-018-2180-0 · Cited by 39 · see citing works
Sokhi, U. K., Liber, M. P., Frye, L., Park, S., Kang, K., Pannellini, T., Zhao, B., Norinsky, R., Ivashkiv, L. B., & Gong, S. (2018) · Nature Communications · doi:10.1038/s41467-018-03081-7 · Cited by 37 · see citing works
Microbial signals, MyD88, and lymphotoxin drive TNF-independent intestinal epithelial tissue damage
Rusu, I., Mennillo, E., Li, Z., Bain, J. L., Sun, X., Ly, K., Rosli, Y. Y., Naser, M., Wang, Z., Advincula, R., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci154993 · Cited by 36 · see citing works
Mele, A. A., Revuelta‐Cervantes, J., Chien, V., Friedman, D. J., & Ferran, C. J. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-0398-6_10 · Cited by 35 · see citing works
Ray-Jones, H., Duffus, K., McGovern, A., Martin, P., Shi, C., Hankinson, J., Gough, O., Yarwood, A., Morris, A. P., Adamson, A., et al. (2020) · BMC Biology · doi:10.1186/s12915-020-00779-3 · Cited by 31 · see citing works
Self-citationLiu, X., Xing, H., Gao, W., Yu, D., Zhao, Y., Shi, X., Zhang, K., Li, P., Yu, J., Xu, W., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-17931-9 · Cited by 29 · see citing works
Self-citationWu, J., Yang, S., Yu, D., Gao, W., Liu, X., Zhang, K., Fu, X., Bao, W., Zhang, K., Yu, J., et al. (2018) · Genes and Immunity · doi:10.1038/s41435-018-0011-6 · Cited by 28 · see citing works
Self-citationKim, T., Bae, S., & Kang, C. (2020) · Arthritis Research & Therapy · doi:10.1186/s13075-020-02181-4 · Cited by 27 · see citing works
Hagberg, N., Lundtoft, C., & Rönnblom, L. (2020) · Scandinavian Journal of Immunology · doi:10.1111/sji.12894 · Cited by 23 · see citing works
Studer, P., da Silva, C. G., Revuelta‐Cervantes, J., Mele, A. A., Csizmadia, E., Siracuse, J. J., Damrauer, S. M., Peterson, C. R., Candinas, D., Stroka, D., et al. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2015.52 · Cited by 22 · see citing works
Hypomorphic A20 expression confers susceptibility to psoriasis
Aki, A., Nagasaki, M., Malynn, B. A., Ma, A. I., & Kagari, T. (2017) · PLoS ONE · doi:10.1371/journal.pone.0180481 · Cited by 22 · see citing works
Tessier‐Cloutier, B., Twa, D. D. W., Baecklund, E., Gascoyne, R. D., Johnson, N. A., Backlin, C., Kamen, D. L., Clarke, A. E., Ramsey‐Goldman, R., Lee, J. L. F., et al. (2019) · Lupus Science & Medicine · doi:10.1136/lupus-2019-000324 · Cited by 22 · see citing works
Low TNFAIP3 expression in psoriatic skin promotes disease susceptibility and severity
Sahloul, N. Y., Mostafa, M. S., Madkour, L. A. E.-F., & Salama, D. (2019) · PLoS ONE · doi:10.1371/journal.pone.0217352 · Cited by 21 · see citing works
From association to mechanism in complex disease genetics: the role of the 3D genome
Fu, Y., Tessneer, K. L., Li, C., & Gaffney, P. M. (2018) · Arthritis Research & Therapy · doi:10.1186/s13075-018-1721-x · Cited by 21 · see citing works
Self-citationTNFAIP3 Plays a Role in Aging of the Hematopoietic System
Smith, M. A., Culver‐Cochran, A. E., Adelman, E. R., Rhyasen, G. W., Ma, A. I., Figueroa, M. E., & Starczynowski, D. T. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.536442 · Cited by 20 · see citing works
Three Chinese pedigrees of A20 haploinsufficiency: clinical, cytokine and molecular characterization
Tian, Y., Wu, B., Peng, L., Wang, J., & Shen, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.955079 · Cited by 15 · see citing works
Han, J., Wang, Y., Li, H., Alateng, C., Bai, Y., Sun, Z., Lv, X., & Wu, R. ‐. (2016) · International Journal of Immunogenetics · doi:10.1111/iji.12250 · Cited by 15 · see citing works
Identification of rheumatoid arthritis causal genes using functional genomics
Ding, J., & Orozco, G. (2019) · Scandinavian Journal of Immunology · doi:10.1111/sji.12753 · Cited by 14 · see citing works
Systemic lupus erythematosus variants modulate the function of an enhancer upstream of TNFAIP3
Pasula, S., Gopalakrishnan, J., Fu, Y., Tessneer, K. L., Wiley, M. M., Pelikan, R. C., Kelly, J. A., & Gaffney, P. M. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.1011965 · Cited by 14 · see citing works
Self-citationDeng, Y., & Tsao, B. P. (2019) · Elsevier eBooks · doi:10.1016/b978-0-323-47927-1.00005-0 · Cited by 14 · see citing works
Smolińska, M., Grzanka, D., Antosik, P., Kasperska, A., Neska−Długosz, I., Jóźwicki, J., & Klimaszewska‐Wiśniewska, A. (2019) · Disease Markers · doi:10.1155/2019/6315936 · Cited by 13 · see citing works
Mistuned NF-κB signaling in lymphocytes: lessons from relevant inborn errors of immunity
Dabbah‐Krancher, G., & Snow, A. L. (2023) · Clinical & Experimental Immunology · doi:10.1093/cei/uxad006 · Cited by 12 · see citing works
3D genome organization and epigenetic regulation in autoimmune diseases
Qiu, Y., Feng, D., Jiang, W., Zhang, T., Lu, Q., & Zhao, M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1196123 · Cited by 12 · see citing works
Yu, W., Zhang, K., Wang, Z., Zhang, J., Chen, T., & Jin, L. (2017) · Human Immunology · doi:10.1016/j.humimm.2017.01.002 · Cited by 12 · see citing works
Shi, X., Qian, T., Li, M., Chen, F., Chen, Y., & Hao, F. (2015) · Immunological Investigations · doi:10.3109/08820139.2015.1037957 · Cited by 11 · see citing works
Pasula, S., Tessneer, K. L., Fu, Y., Gopalakrishnan, J., Pelikan, R. C., Kelly, J. A., Wiley, G. B., Wiley, M. M., & Gaffney, P. M. (2019) · Arthritis & Rheumatology · doi:10.1002/art.41188 · Cited by 11 · see citing works
Self-citationE3 Ubiquitin Ligases: Structures, Biological Functions, Diseases, and Therapy
Wang, H., Peng, J., Li, H., Lan, Y., Guo, J., Qiu, Q., & Huang, X. (2025) · MedComm · doi:10.1002/mco2.70528 · Cited by 10 · see citing works
Daems, C., Sekulić, M., Vulsteke, V., Loo, G., D’Hooge, R., Callaerts‐Vegh, Z., & Callaerts, P. (2019) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2019.100018 · Cited by 9 · see citing works
Preserving immune homeostasis with A20
Razani, B., Malynn, B. A., & Ma, A. I. (2020) · Advances in immunology · doi:10.1016/bs.ai.2020.10.001 · Cited by 9 · see citing works
Dabbah‐Krancher, G., Ruchinskas, A. J., Kallarakal, M. A., Lee, K. P., Bauman, B. M., Epstein, B. E., Yin, H., Krappmann, D., Schaefer, B. C., & Snow, A. L. (2024) · European Journal of Immunology · doi:10.1002/eji.202451245 · Cited by 8 · see citing works
Can chromatin conformation technologies bring light into human molecular pathology?
Kubiak, M., & Lewandowska, M. A. (2015) · Acta Biochimica Polonica · doi:10.18388/abp.2015_984 · Cited by 8 · see citing works
Potteti, H. R., Venkareddy, L. K., Noone, P. M., Ankireddy, A., Tamatam, C. R., Mehta, D., Tiruppathì, C., & Reddy, S. P. (2021) · Antioxidants · doi:10.3390/antiox10060847 · Cited by 8 · see citing works
Zhang, P., Li, N., Zhu, Q., Li, F., Yang, C., Zeng, X., Lv, Y., Zhou, Z.-H., Han, Q., & Liu, Z. (2015) · Virology Journal · doi:10.1186/s12985-015-0268-6 · Cited by 7 · see citing works
Sato, J., Azuma, K., Kinowaki, K., Ikeda, K., Ogura, T., Takazawa, Y., Kawabata, H., Kitagawa, M., & Inoue, S. (2020) · Pathology International · doi:10.1111/pin.13047 · Cited by 7 · see citing works
Rahimov, F., Ghosh, S., Petiwala, S. M., Schmidt, M., Nyamugenda, E., Shi, M., Tam, J. W., Verduzco, D., Singh, S., Avram, V., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65277-y · Cited by 6 · see citing works
Li, N., Shi, Y., Zhang, P., Sang, J., Li, F., Deng, H., Lv, Y., Han, Q., & Liu, Z. (2017) · Virology Journal · doi:10.1186/s12985-017-0814-5 · Cited by 6 · see citing works
Liufu, R., Chen, Y., Wang, J., Wang, Y.-Y.-Q., Wu, Y., Jiang, W., Wang, C., Peng, J., Weng, L., & Du, B. (2024) · Critical Care Medicine · doi:10.1097/ccm.0000000000006523 · Cited by 5 · see citing works
Tobias, R., Kumar, S., Liu, J., Lenci, N., Gharabi, A., Stibor, D., Advincula, R., Achacoso, P., Huang, Z., Bowman, C., et al. (2025) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2025.03.043 · Cited by 5 · see citing works
Kubiak, M., Jurek, A., Kaminska, K. H., Kowalewski, J., Huang, S., & Lewandowska, M. A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020242 · Cited by 5 · see citing works
Lou, L., Bao, W., Liu, X., Song, H., Wang, Y., Zhang, K., Gao, W., Li, H., Tu, Z., & Wang, S. (2018) · Journal of Clinical Microbiology · doi:10.1128/jcm.01363-17 · Cited by 4 · see citing works
Self-citationGenes and genetics in human SLE
Richard, M. L., & Tsao, B. P. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-814551-7.00011-8 · Cited by 4 · see citing works
Opportunity to improve livestock traits using 3D genomics
MacPhillamy, C., Pitchford, W. S., Alinejad‐Rokny, H., & Low, W. Y. (2021) · Animal Genetics · doi:10.1111/age.13135 · Cited by 4 · see citing works
Xu, M., Gao, W., Wu, L., Liu, X., Yu, D., Shi, X., Liu, X., Wang, Q., Fu, X., Yu, J., et al. (2018) · Human Immunology · doi:10.1016/j.humimm.2018.11.008 · Cited by 4 · see citing works
Self-citationPapanicolaou, N., & Bonetti, A. (2020) · SLAS DISCOVERY · doi:10.1177/2472555220926158 · Cited by 4 · see citing works
Non-coding DNA variants for risk in lupus
Zhang, Y., Hou, G., & Shen, N. (2024) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2024.101937 · Cited by 2 · see citing works
Genes and Genetics in Human Systemic Lupus Erythematosus
Deng, Y., & Tsao, B. P. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801917-7.00010-3 · Cited by 2 · see citing works
Warner, J. D., Wiley, M. M., Wu, Y.-Y., Wen, F., Kinter, M. T., Yanagiya, A., Tessneer, K. L., & Gaffney, P. M. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/163998 · Cited by 2 · see citing works
Self-citationSusceptibilidad genética y enfermedad autoinmune reumática: Revisión narrativa
Herrera, M. A. (2021) · Ciencia Tecnología y Salud · doi:10.36829/63cts.v8i1.907 · Cited by 1 · see citing works
Functional genomics of the VNN1 gene
Diepeveen, L. A. (2013) · UWA Profiles and Research Repository (UWA)
Determining the role of the IL2 pathway in susceptibility to juvenile idiopathic arthritis
Taylor, C. J. (2018) · Research Explorer (The University of Manchester)
Bakr, A., Zedan, M. M., Attia, Z. R., Mutawi, T. M., & Shehawy, A. S. E. (2021) · Alexandria Journal of Pediatrics · doi:10.4103/ajop.ajop_8_21
Lessard, C. J., Tessneer, K. L., & Tsao, B. P. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820583-9.00005-1
Genetic alterations leading to autoimmunity
Tessneer, K. L., Kelly, J. A., & Gaffney, P. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23947-2.00026-6
Self-citationA New Mouse Model of Psoriatic Arthritis
Razani, B., Chandran, V., de Vlam, K., Liao, W. J., Malynn, B. A., & Ma, A. I. (2025) · The Journal of Rheumatology · doi:10.3899/jrheum.2025-0528
A rare human TNFAIP3 variant reveals how A20 abundance is regulated by TAX1BP1Preprint
Lee, C. E., Downes, M. B., Chand, R., Horikawa, K., Athanasopoulos, V., Miraghazadeh, B., & Cook, M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.25.714162
Genes and genetics in human SLE
Scofield, R. H., & Ice, J. A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-33957-8.00014-7
- Authors
- Wang, S., Wen, F., Wiley, G. B., Kinter, M. T., & Gaffney, P. M.
- Affiliations
- Oklahoma Medical Research Foundation (US)
- Corresponding author
- Gaffney, Patrick M.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-09-05
- Volume
- 9
- Issue
- 9
- Pages
- e1003750
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC3764111
- OpenAlex
- W2032639657
- Cited by
- 98
- References
- 40
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 11 · 2019: 13 · 2018: 9 · 2017: 9 · 2016: 8 · 2015: 9 · 2014: 7 · 2013: 1 · 2012: 1
- FWCI
- 6.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Oklahoma Medical Research Foundation
- National Institutes of Health (5rc2ar058959-02, AR058959, AI063274, GM103456)
- National Institute of General Medical Sciences (P20GM103456, GM103456)
- National Institute of Allergy and Infectious Diseases (R01AI063274, AI-063274, R56AI063274)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-063124, AR056360, R01AR063124, RC2-AR-058959, AR058959, R01AR056360)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- systemic lupus erythematosus, A20, enhancers, causal variants, risk haplotype, NF-kappaB binding, SATB1, enhancer-promoter interactions, transcriptional regulation, ubiquitin-editing enzyme, NF-κB signaling
- MeSH terms
- Tumor Necrosis Factor alpha-Induced Protein 3, Alleles, DNA-Binding Proteins, Enhancer Elements, Genetic, Gene Expression Regulation, Haplotypes, Humans, Lupus Erythematosus, Systemic, Nuclear Proteins, Promoter Regions, Genetic, Signal Transduction, NF-kappa B, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Matrix Attachment Region Binding Proteins, Intracellular Signaling Peptides and Proteins, HEK293 Cells
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