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22-03-2024 | Ankylosing Spondylitis | RESEARCH

The Role of H3K27me3-Mediated Th17 Differentiation in Ankylosing Spondylitis

Authors: Yuening Chen, Wanlin Liu, Xiaohan Xu, Hongying Zhen, Bo Pang, Zhe Zhao, Yanan Zhao, Hongxiao Liu

Abstract

Ankylosing spondylitis (AS) is a common chronic progressive inflammatory autoimmune disease. T helper 17 (Th17) cells are the major effector cells mediating AS inflammation. Histone 3 Lys 27 trimethylation (H3K27me3) is an inhibitory histone modification that silences gene transcription and plays an important role in Th17 differentiation. The objective of this study was to investigate the expression of H3K27me3 in patients with AS and to explore its epigenetic regulation mechanism of Th17 differentiation during AS inflammation. We collected serum samples from 45 patients with AS at various stages and 10 healthy controls to measure their Interleukin-17 (IL-17) levels using ELISA. A quantitative polymerase chain reaction was used to quantify the mRNA levels of RORc and the signaling molecules of the JAK2/STAT3 pathway, JMJD3, and EZH2. Additionally, Western blot analysis was performed to quantify the protein levels of H3K27me3, RORγt, JAK2, STAT3, JMJD3, and EZH2 in cell protein extracts. The results showed that H3K27me3 expression in peripheral blood mononuclear cells (PBMCs) was significantly lower in patients with active AS compared to both the normal control groups and those with stable AS. Moreover, a significant negative correlation was observed between H3K27me3 expression and the characteristic transcription factor of Th17 differentiation, RORγt. We also discovered that patients with active AS exhibited significantly higher levels of JMJD3, an inhibitor of H3K27 demethylase, compared to the normal control group and patients with stable AS, while the expression of H3K27 methyltransferase (EZH2) was significantly lower. These findings suggest that H3K27me3 may be a dynamic and important epigenetic modification in AS inflammation, and JMJD3/EZH2 regulates the methylation level of H3K27me3, which may be one of the key regulatory factors in the pathogenesis of AS. These findings contribute to our understanding of the role of epigenetics in AS and may have implications for the development of novel therapeutic strategies for AS.

Braun, J., and J. Sieper. 2007. Ankylosing spondylitis. Lancet 369 (9570): 1379–1390.PubMedCrossRef

Maksymowych, W.P. 2010. Disease modification in ankylosing spondylitis. Nature Reviews Rheumatology 6 (2): 75–81.PubMedCrossRef

Navarro-Compán, V., A. Sepriano, B. El-Zorkany, and D. van der Heijde. 2021. Axial spondyloarthritis. Annals of the Rheumatic Diseases 80 (12): 1511–1521.PubMedCrossRef

Liu, L., Y. Yuan, S. Zhang, J. Xu, and J. Zou. 2021. Osteoimmunological insights into the pathogenesis of ankylosing spondylitis. Journal of Cellular Physiology 236 (9): 6090–6100.PubMedCrossRef

Miossec, P., and J.K. Kolls. 2012. Targeting IL-17 and TH17 cells in chronic inflammation. Nature Reviews Drug Discovery 11 (10): 763–776.PubMedCrossRef

Yang, J., M.S. Sundrud, J. Skepner, and T. Yamagata. 2014. Targeting Th17 cells in autoimmune diseases. Trends in Pharmacological Sciences 35 (10): 493–500.PubMedCrossRef

Gracey, E., Y. Yao, B. Green, Z. Qaiyum, Y. Baglaenko, A. Lin, A. Anton, R. Ayearst, P. Yip, and R.D. Inman. 2016. Sexual dimorphism in the Th17 signature of ankylosing spondylitis. Arthritis & Rheumatology (Hoboken, NJ) 68 (3): 679–689.CrossRef

Klasen, C., A. Meyer, P.S. Wittekind, I. Waqué, S. Nabhani, and D.M. Kofler. 2019. Prostaglandin receptor EP4 expression by Th17 cells is associated with high disease activity in ankylosing spondylitis. Arthritis Research & Therapy 21 (1): 159.CrossRef

Gaston, J.S.H., and D.R. Jadon. 2017. Th17 cell responses in spondyloarthritis. Best practice & research Clinical Rheumatology 31 (6): 777–796.CrossRef

10.

Chen, L., M.H. Al-Mossawi, A. Ridley, T. Sekine, A. Hammitzsch, J. de Wit, D. Simone, H. Shi, F. Penkava, M. Kurowska-Stolarska, et al. 2017. miR-10b-5p is a novel Th17 regulator present in Th17 cells from ankylosing spondylitis. Annals of the Rheumatic Diseases 76 (3): 620–625.PubMedCrossRef

11.

McGinty, J., N. Brittain, and T.J. Kenna. 2020. Looking beyond Th17 cells: A role for Tr1 cells in ankylosing spondylitis? Frontiers in Immunology 11: 608900.PubMedPubMedCentralCrossRef

12.

Pedersen, S.J., and W.P. Maksymowych. 2018. Beyond the TNF-α inhibitors: New and emerging targeted therapies for patients with axial spondyloarthritis and their relation to pathophysiology. Drugs 78 (14): 1397–1418.PubMedCrossRef

13.

Baeten, D., J. Sieper, J. Braun, X. Baraliakos, M. Dougados, P. Emery, A. Deodhar, B. Porter, R. Martin, M. Andersson, et al. 2015. Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. The New England Journal of Medicine 373 (26): 2534–2548.PubMedCrossRef

14.

Antignano, F., and C. Zaph. 2015. Regulation of CD4 T-cell differentiation and inflammation by repressive histone methylation. Immunology and Cell Biology 93 (3): 245–252.PubMedCrossRef

15.

Del Vescovo, S., V. Venerito, C. Iannone, and G. Lopalco. 2023. Uncovering the underworld of axial spondyloarthritis. International Journal of Molecular Sciences 24 (7): 6463.PubMedPubMedCentralCrossRef

16.

Roudier, F., I. Ahmed, C. Berard, A. Sarazin, T. Mary-Huard, S. Cortijo, D. Bouyer, E. Caillieux, E. Duvernois-Berthet, L. Al-Shikhley, et al. 2011. Integrative epigenomic mapping defines four main chromatin states in arabidopsis. The EMBO Journal 30 (10): 1928–1938.PubMedPubMedCentralCrossRef

17.

Tang, H., S. An, H. Zhen, and F. Chen. 2014. Characterization of combinatorial histone modifications on lineage-affiliated genes during hematopoietic stem cell myeloid commitment. Acta Biochimica et Biophysica Sinica 46 (10): 894–901.PubMedCrossRef

18.

Zhang, X., H. Wen, and X. Shi. 2012. Lysine methylation: Beyond histones. Acta Biochimica et Biophysica Sinica 44 (1): 14–27.PubMedCrossRef

19.

Agger, K., P.A. Cloos, J. Christensen, D. Pasini, S. Rose, J. Rappsilber, I. Issaeva, E. Canaani, A.E. Salcini, and K. Helin. 2007. UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature 449 (7163): 731–734.PubMedCrossRef

20.

Schuettengruber, B., H.M. Bourbon, L. Di Croce, and G. Cavalli. 2017. Genome regulation by polycomb and trithorax: 70 years and counting. Cell 171 (1): 34–57.PubMedCrossRef

21.

Hubner, M.R., and D.L. Spector. 2010. Role of H3K27 demethylases Jmjd3 and UTX in transcriptional regulation. Cold Spring Harbor Symposia on Quantitative Biology 75: 43–49.PubMedCrossRef

22.

Duan, R., W. Du, and W. Guo. 2020. EZH2: A novel target for cancer treatment. Journal of Hematology & Oncology 13 (1): 104.CrossRef

23.

Hoffmann, F., D. Niebel, P. Aymans, S. Ferring-Schmitt, D. Dietrich, and J. Landsberg. 2020. H3K27me3 and EZH2 expression in melanoma: Relevance for melanoma progression and response to immune checkpoint blockade. Clinical Epigenetics 12 (1): 24.PubMedPubMedCentralCrossRef

24.

Liu, Z., W. Cao, L. Xu, X. Chen, Y. Zhan, Q. Yang, S. Liu, P. Chen, Y. Jiang, X. Sun, et al. 2015. The histone H3 lysine-27 demethylase Jmjd3 plays a critical role in specific regulation of Th17 cell differentiation. Journal of Molecular Cell Biology 7 (6): 505–516.PubMedCrossRef

25.

Yang, X.P., K. Jiang, K. Hirahara, G. Vahedi, B. Afzali, G. Sciume, M. Bonelli, H.W. Sun, D. Jankovic, Y. Kanno, et al. 2015. EZH2 is crucial for both differentiation of regulatory T cells and T effector cell expansion. Scientific Reports 5: 10643.PubMedPubMedCentralCrossRef

26.

Guendisch, U., J. Weiss, F. Ecoeur, J.C. Riker, K. Kaupmann, J. Kallen, S. Hintermann, D. Orain, J. Dawson, A. Billich, et al. 2017. Pharmacological inhibition of RORgammat suppresses the Th17 pathway and alleviates arthritis in vivo. PLoS ONE 12 (11): e0188391.PubMedPubMedCentralCrossRef

27.

Unutmaz, D. 2009. RORC2: The master of human Th17 cell programming. European Journal of Immunology 39 (6): 1452–1455.PubMedCrossRef

28.

Huh, J.R., M.W. Leung, P. Huang, D.A. Ryan, M.R. Krout, R.R. Malapaka, J. Chow, N. Manel, M. Ciofani, S.V. Kim, et al. 2011. Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORgammat activity. Nature 472 (7344): 486–490.PubMedPubMedCentralCrossRef

29.

Xia, L., E. Tian, M. Yu, C. Liu, L. Shen, Y. Huang, Z. Wu, J. Tian, K. Yu, Y. Wang, et al. 2022. RORγt agonist enhances anti-PD-1 therapy by promoting monocyte-derived dendritic cells through CXCL10 in cancers. Journal of Experimental & Clinical Cancer Research : CR 41 (1): 155.PubMedCentralCrossRef

30.

Yahia-Cherbal, H., M. Rybczynska, D. Lovecchio, T. Stephen, C. Lescale, K. Placek, J. Larghero, L. Rogge, and E. Bianchi. 2019. NFAT primes the human RORC locus for RORγt expression in CD4+ T cells. Nature Communications 10 (1): 4698.PubMedPubMedCentralCrossRef

31.

Chaudhry, A., D. Rudra, P. Treuting, R.M. Samstein, Y. Liang, A. Kas, and A.Y. Rudensky. 2009. CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 326 (5955): 986–991.PubMedPubMedCentralCrossRef

32.

Burchfield, J.S., Q. Li, H.Y. Wang, and R.F. Wang. 2015. JMJD3 as an epigenetic regulator in development and disease. The International Journal of Biochemistry & Cell Biology 67: 148–157.CrossRef

33.

Cohen, C.J., S.Q. Crome, K.G. MacDonald, E.L. Dai, D.L. Mager, and M.K. Levings. 2011. Human Th1 and Th17 cells exhibit epigenetic stability at signature cytokine and transcription factor loci. Journal of Immunology 187 (11): 5615–5626.CrossRef

34.

Hanisch, U.K. 2014. Linking STAT and TLR signaling in microglia: A new role for the histone demethylase Jmjd3. Journal of Molecular Medicine 92 (3): 197–200.PubMedCrossRef

35.

Taams, L.S., K.J.A. Steel, U. Srenathan, L.A. Burns, and B.W. Kirkham. 2018. IL-17 in the immunopathogenesis of spondyloarthritis. Nature Reviews Rheumatology 14 (8): 453–466.PubMedCrossRef

36.

Cua, D.J., and C.M. Tato. 2010. Innate IL-17-producing cells: The sentinels of the immune system. Nature Reviews Immunology 10 (7): 479–489.PubMedCrossRef

37.

Zrioual, S., R. Ecochard, A. Tournadre, V. Lenief, M.A. Cazalis, and P. Miossec. 2009. Genome-wide comparison between IL-17A- and IL-17F-induced effects in human rheumatoid arthritis synoviocytes. Journal of Immunology 182 (5): 3112–3120.CrossRef

38.

Geng, J., S. Yu, H. Zhao, X. Sun, X. Li, P. Wang, X. Xiong, L. Hong, C. Xie, J. Gao, et al. 2017. The transcriptional coactivator TAZ regulates reciprocal differentiation of T(H)17 cells and T(reg) cells. Nature Immunology 18 (7): 800–812.PubMedCrossRef

39.

Ivanov, I.I., B.S. McKenzie, L. Zhou, C.E. Tadokoro, A. Lepelley, J.J. Lafaille, D.J. Cua, and D.R. Littman. 2006. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126 (6): 1121–1133.PubMedCrossRef

40.

Zhang, M., L. Zhou, Y. Xu, M. Yang, Y. Xu, G.P. Komaniecki, T. Kosciuk, X. Chen, X. Lu, X. Zou, et al. 2020. A STAT3 palmitoylation cycle promotes T(H)17 differentiation and colitis. Nature 586 (7829): 434–439.PubMedPubMedCentralCrossRef

41.

Lee, J.Y., J.A. Hall, L. Kroehling, L. Wu, T. Najar, H.H. Nguyen, W.Y. Lin, S.T. Yeung, H.M. Silva, D. Li, et al. 2020. Serum amyloid A proteins induce pathogenic Th17 cells and promote inflammatory disease. Cell 180 (1): 79-91.e16.PubMedCrossRef

42.

de Vlam, K. 2010. Soluble and tissue biomarkers in ankylosing spondylitis. Best Practice & Research Clinical Rheumatology 24 (5): 671–682.PubMedCrossRef

43.

Jiang, Y., C. Xiang, F. Zhong, Y. Zhang, L. Wang, Y. Zhao, J. Wang, C. Ding, L. Jin, F. He, et al. 2021. Histone H3K27 methyltransferase EZH2 and demethylase JMJD3 regulate hepatic stellate cells activation and liver fibrosis. Theranostics 11 (1): 361–378.PubMedPubMedCentralCrossRef

44.

Li, Q., J. Zou, M. Wang, X. Ding, I. Chepelev, X. Zhou, W. Zhao, G. Wei, J. Cui, K. Zhao, et al. 2014. Critical role of histone demethylase Jmjd3 in the regulation of CD4+ T-cell differentiation. Nature Communications 5: 5780.PubMedCrossRef

45.

Cribbs, A.P., S. Terlecki-Zaniewicz, M. Philpott, J. Baardman, D. Ahern, M. Lindow, S. Obad, H. Oerum, B. Sampey, P.K. Mander, et al. 2020. Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism. Proceedings of the National Academy of Sciences of the United States of America 117 (11): 6056–6066.PubMedPubMedCentralCrossRef

46.

Chen, Q., X. Duan, M. Xu, H. Fan, Y. Dong, H. Wu, M. Zhang, Y. Liu, Z. Nan, S. Deng, et al. 2020. BMSC-EVs regulate Th17 cell differentiation in UC via H3K27me3. Molecular Immunology 118: 191–200.PubMedCrossRef

47.

Liu, X., S. Ren, X. Qu, C. Ge, K. Cheng, and R.C. Zhao. 2015. Mesenchymal stem cells inhibit Th17 cells differentiation via IFN-γ-mediated SOCS3 activation. Immunologic Research 61 (3): 219–229.PubMedCrossRef

48.

Lu, Y., Q. Ma, L. Yu, H. Huang, X. Liu, P. Chen, H. Ran, and W. Liu. 2023. JAK2 inhibitor ameliorates the progression of experimental autoimmune myasthenia gravis and balances Th17/Treg cells via regulating the JAK2/STAT3-AKT/mTOR signaling pathway. International Immunopharmacology 115: 109693.PubMedCrossRef

49.

He, L., J. Du, Y. Chen, C. Liu, M. Zhou, S. Adhikari, D.T. Rubin, J. Pekow, and Y.C. Li. 2019. Renin-angiotensin system promotes colonic inflammation by inducing T(H)17 activation via JAK2/STAT pathway. American Journal of Physiology Gastrointestinal and Liver Physiology 316 (6): G774–G784.PubMedPubMedCentralCrossRef

50.

Raychaudhuri, S.P., and S.K. Raychaudhuri. 2017. Mechanistic rationales for targeting interleukin-17A in spondyloarthritis. Arthritis Research & Therapy 19 (1): 51.CrossRef

51.

Lubberts, E. 2015. The IL-23-IL-17 axis in inflammatory arthritis. Nature Reviews Rheumatology 11 (7): 415–429.PubMedCrossRef

52.

Dubash, S., C. Bridgewood, D. McGonagle, and H. Marzo-Ortega. 2019. The advent of IL-17A blockade in ankylosing spondylitis: Secukinumab, ixekizumab and beyond. Expert Review of Clinical Immunology 15 (2): 123–134.PubMedCrossRef

53.

Guo, P., Y. Liu, F. Geng, A.W. Daman, X. Liu, L. Zhong, A. Ravishankar, R. Lis, J.G. Barcia Durán, T. Itkin, et al. 2022. Histone variant H3.3 maintains adult haematopoietic stem cell homeostasis by enforcing chromatin adaptability. Nature Cell Biology 24 (1): 99–111.PubMedCrossRef

54.

Wang, Y., P. Deng, Y. Liu, Y. Wu, Y. Chen, Y. Guo, S. Zhang, X. Zheng, L. Zhou, W. Liu, et al. 2020. Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations. Nature Communications 11 (1): 5596.PubMedPubMedCentralCrossRef

55.

Nassiri, F., J.Z. Wang, O. Singh, S. Karimi, T. Dalcourt, N. Ijad, N. Pirouzmand, H.K. Ng, A. Saladino, B. Pollo, et al. 2021. Loss of H3K27me3 in meningiomas. Neuro-Oncology 23 (8): 1282–1291.PubMedPubMedCentralCrossRef

56.

Behling, F., C. Fodi, I. Gepfner-Tuma, K. Kaltenbach, M. Renovanz, F. Paulsen, M. Skardelly, J. Honegger, M. Tatagiba, J. Schittenhelm, et al. 2021. H3K27me3 loss indicates an increased risk of recurrence in the Tübingen meningioma cohort. Neuro-Oncology 23 (8): 1273–1281.PubMedCrossRef

57.

Abu-Hanna, J., J.A. Patel, E. Anastasakis, R. Cohen, L.H. Clapp, M. Loizidou, and M.M.R. Eddama. 2022. Therapeutic potential of inhibiting histone 3 lysine 27 demethylases: A review of the literature. Clinical Epigenetics 14 (1): 98.PubMedPubMedCentralCrossRef

58.

Zhang, X., L. Liu, X. Yuan, Y. Wei, and X. Wei. 2019. JMJD3 in the regulation of human diseases. Protein & Cell 10 (12): 864–882.CrossRef

59.

Jin, Y., Z. Liu, Z. Li, H. Li, C. Zhu, R. Li, T. Zhou, and B. Fang. 2022. Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1. International Journal of Oral Science 14 (1): 34.PubMedPubMedCentralCrossRef

60.

Nakka, K., S. Hachmer, Z. Mokhtari, R. Kovac, H. Bandukwala, C. Bernard, Y. Li, G. Xie, C. Liu, M. Fallahi, et al. 2022. JMJD3 activated hyaluronan synthesis drives muscle regeneration in an inflammatory environment. Science 377 (6606): 666–669.PubMedCrossRef

61.

Sun, D., X. Cao, and C. Wang. 2019. Polycomb chromobox Cbx2 enhances antiviral innate immunity by promoting Jmjd3-mediated demethylation of H3K27 at the Ifnb promoter. Protein & Cell 10 (4): 285–294.CrossRef

62.

Davis, F.M., L.C. Tsoi, W.J. Melvin, A. denDekker, R. Wasikowski, A.D. Joshi, S. Wolf, A.T. Obi, A.C. Billi, X. Xing, et al. 2021. Inhibition of macrophage histone demethylase JMJD3 protects against abdominal aortic aneurysms. The Journal of Experimental Medicine 218 (6): e20201839.PubMedPubMedCentralCrossRef

63.

Leng, X.Y., J. Yang, H. Fan, Q.Y. Chen, B.J. Cheng, H.X. He, F. Gao, F. Zhu, T. Yu, and Y.J. Liu. 2022. JMJD3/H3K27me3 epigenetic modification regulates Th17/Treg cell differentiation in ulcerative colitis. International Immunopharmacology 110: 109000.PubMedCrossRef

64.

Ruutu, M., G. Thomas, R. Steck, M.A. Degli-Esposti, M.S. Zinkernagel, K. Alexander, J. Velasco, G. Strutton, A. Tran, H. Benham, et al. 2012. β-glucan triggers spondylarthritis and Crohn’s disease-like ileitis in SKG mice. Arthritis and Rheumatism 64 (7): 2211–2222.PubMedCrossRef

65.

Zhai, Y., L. Chen, Q. Zhao, Z.H. Zheng, Z.N. Chen, H. Bian, X. Yang, H.Y. Lu, P. Lin, X. Chen, et al. 2023. Cysteine carboxyethylation generates neoantigens to induce HLA-restricted autoimmunity. Science 379 (6637): eabg2482.PubMedCrossRef

66.

Kucuksezer, U.C., E. Aktas Cetin, F. Esen, I. Tahrali, N. Akdeniz, M.Y. Gelmez, and G. Deniz. 2021. The role of natural killer cells in autoimmune diseases. Frontiers in Immunology 12: 622306.PubMedPubMedCentralCrossRef

67.

Przanowski, P., M. Dabrowski, A. Ellert-Miklaszewska, M. Kloss, J. Mieczkowski, B. Kaza, A. Ronowicz, F. Hu, A. Piotrowski, H. Kettenmann, et al. 2014. The signal transducers Stat1 and Stat3 and their novel target Jmjd3 drive the expression of inflammatory genes in microglia. Journal of Molecular Medicine 92 (3): 239–254.PubMedCrossRef

68.

Yamaguchi, H., and M.C. Hung. 2014. Regulation and role of EZH2 in cancer. Cancer Research and Treatment 46 (3): 209–222.PubMedPubMedCentralCrossRef

69.

Lund, K., P.D. Adams, and M. Copland. 2014. EZH2 in normal and malignant hematopoiesis. Leukemia 28 (1): 44–49.PubMedCrossRef

70.

Zhang, Y., S. Kinkel, J. Maksimovic, E. Bandala-Sanchez, M.C. Tanzer, G. Naselli, J.G. Zhang, Y. Zhan, A.M. Lew, J. Silke, et al. 2014. The polycomb repressive complex 2 governs life and death of peripheral T cells. Blood 124 (5): 737–749.PubMedCrossRef

71.

Fan, K., C.L. Zhang, B.H. Zhang, M.Q. Gao, and Y.C. Sun. 2022. Analysis of the correlation between Zeste enhancer homolog 2 (EZH2) mRNA expression and the prognosis of mesothelioma patients and immune infiltration. Scientific Reports 12 (1): 16583.PubMedPubMedCentralCrossRef

72.

Coit, P., M.G. Dozmorov, J.T. Merrill, W.J. McCune, K. Maksimowicz-McKinnon, J.D. Wren, and A.H. Sawalha. 2016. Epigenetic reprogramming in naive CD4+ T cells favoring T cell activation and non-Th1 effector T cell immune response as an early event in lupus flares. Arthritis & Rheumatology (Hoboken, NJ) 68 (9): 2200–2209.CrossRef

73.

Maeda, M., H. Takeshima, N. Iida, N. Hattori, S. Yamashita, H. Moro, Y. Yasukawa, K. Nishiyama, T. Hashimoto, S. Sekine, et al. 2020. Cancer cell niche factors secreted from cancer-associated fibroblast by loss of H3K27me3. Gut 69 (2): 243–251.PubMedCrossRef

74.

Gauchotte, G., M. Peyre, C. Pouget, D. Cazals-Hatem, M. Polivka, F. Rech, P. Varlet, H. Loiseau, S. Lacomme, K. Mokhtari, et al. 2020. Prognostic value of histopathological features and loss of H3K27me3 immunolabeling in anaplastic meningioma: A multicenter retrospective study. Journal of Neuropathology and Experimental Neurology 79 (7): 754–762.PubMedCrossRef

75.

Harutyunyan, A.S., B. Krug, H. Chen, S. Papillon-Cavanagh, M. Zeinieh, N. De Jay, S. Deshmukh, C.C.L. Chen, J. Belle, L.G. Mikael, et al. 2019. H3K27M induces defective chromatin spread of PRC2-mediated repressive H3K27me2/me3 and is essential for glioma tumorigenesis. Nature Communications 10 (1): 1262.PubMedPubMedCentralCrossRef

Title: The Role of H3K27me3-Mediated Th17 Differentiation in Ankylosing Spondylitis
Authors: Yuening Chen
Wanlin Liu
Xiaohan Xu
Hongying Zhen
Bo Pang
Zhe Zhao
Yanan Zhao
Hongxiao Liu
Publication date: 22-03-2024
Publisher: Springer US
Keywords: Ankylosing Spondylitis
Epigenetics
Published in: Inflammation
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-024-02002-9

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