title: Demethylation of the FCER1G promoter leads to FcεRI overexpression on monocytes of patients with atopic dermatitis.
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.
  
  
  CONCLUSIONS
  Demethylation of specific regulatory elements within the FCER1G locus contributes to FcεRI overexpression on monocytes from patients with AD.
authors.affiliation: Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Zhao
authors.forename: G
authors.initials: G
authors.lastname: Liang
authors.forename: H
authors.initials: H
authors.lastname: Yin
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Wen
authors.forename: Q
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000293:Adolescent; D000328:Adult; D019175:DNA Methylation; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C543372:FcepsilonRI gamma-chain, human; D017455:Receptors, IgE; D007073:Immunoglobulin E