Demethylation of the FCER1G promoter leads to FcεRI overexpression on monocytes of patients with atopic dermatitis

Allergy: European Journal of Allergy and Clinical Immunology - Tập 67 Số 3 - Trang 424-430 - 2012
Yong Liang1, P. Wang2, Ming Zhao2, Guobiao Liang2, Heng Yin2, G. Zhang2, Hao Wen2, Qianjin Lu2
1Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology,#N# The Second Xiangya Hospital, Central South University, Changsha,#N# China
2Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China

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To cite this article: Liang Y, Wang P, Zhao M, Liang G, Yin H, Zhang G, Wen H, Lu Q. Demethylation of the FCER1G promoter leads to FcεRI overexpression on monocytes of patients with atopic dermatitis. Allergy 2012; 67: 424–430.Abstract Background:  Overexpression of the high‐affinity receptor for immunoglobulin E on atopic monocytes and dendritic cells is known to contribute to the pathogenesis of atopic dermatitis (AD). However, it remains unclear what is the underlying mechanism of FcεRI deregulation. It has been speculated that epigenetic deregulation may play a role. Methods:  Global DNA methylation levels of monocytes from 10 AD patients and 10 healthy controls were measured using a global DNA methylation kit. Bisulfite sequencing was performed to determine the methylation status of the FCER1G promoter region. FcεRIγ mRNA and FcεRI protein levels were detected by real‐time RT‐PCR, Western blotting, and flow cytometry, respectively. Patch methylation and the demethylating agent, 5‐azacytidine, were used to determine the functional significance of methylation changes on FcεRI expression. Results:  Monocytes from AD patients show a global hypomethylation, as well as a locus‐specific hypomethylation at FCER1G promoter, as compared to healthy controls. Furthermore, this hypomethylation of FCER1G is inversely correlated with its expression. Patch methylation in combination with luciferase reporter assay confirmed the direct relationship between methylation and expression. Moreover, treating healthy monocytes with 5‐azacytidine caused a reduction in methylation levels and an induction in FcεRIγ transcription and surface expression of FcεRI. Conclusion:  Demethylation of specific regulatory elements within the FCER1G locus contributes to FcεRI overexpression on monocytes from patients with AD.

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Tài liệu tham khảo

10.1111/j.1398-9995.2008.01922.x

10.1172/JCI200315932

10.1067/mai.2000.106484

10.1016/j.jaci.2010.07.030

10.1038/nrg887

Brini AT, 1993, Involvement of Alu sequences in the cell‐specific regulation of transcription of the gamma chain of Fc and T cell receptors, J Biol Chem, 268, 1355, 10.1016/S0021-9258(18)54083-7

10.1093/nar/gkr017

10.1001/archderm.135.12.1551

10.1159/000247298

10.3324/haematol.2010.033845

10.1006/meth.2001.1262

10.1251/bpo89

10.1034/j.1398-9995.2002.23737.x

10.1111/j.1399-0039.2008.01068.x

10.1164/rccm.200901-0135OC

10.1016/0092-8674(83)90514-7

10.1016/j.jmb.2004.12.027

10.1074/jbc.274.34.23948

10.1093/toxsci/kfm290

10.1073/pnas.0905063106

10.1002/art.30196

Hollingsworth JW, 2008, In utero supplementation with methyl donors enhances allergic airway disease in mice, J Clin Invest, 118, 3462

10.1136/adc.2008.142448

10.1093/aje/kwp315

10.1016/j.jaci.2009.03.007

10.1093/ije/dyl094

10.1016/j.nut.2007.10.007

10.1093/jn/137.7.1713