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FcRn mediates recycling and transcytosis of IgG and albumin in various cell types. The MHC-class-I-like protein of the FcRn heterodimer is encoded by  FCGRT . Few determinants of variable  FCGRT  expression in humans have been identified so far. In this study, we investigated the presence of DNA methylation in regulatory regions of  FCGRT  in samples of human liver and myocardium tissue, and we examined the impact of  FCGRT  methylation on FcRn expression in model cell lines. Quantitative DNA methylation analysis of the  FCGRT  locus revealed differentially methylated regions in DNA from liver and myocardium. Methylation status in individual CpG sites correlated with  FCGRT  mRNA expression. Data from model cell lines suggest that differential methylation in the −1058 to −587 bp regulatory region of  FCGRT  contributes to FcRn expression. Chromatin immunoprecipitation assays indicate that CpG site methylation impacts the binding of the methylation sensitive transcription factors Zbtb7a and Sp1. This study provides a foundation to further define the contribution of epigenetic factors during the control of FcRn expression and IgG traffic in human tissues.

Contribution of DNA methylation to the expression of FCGRT in human liver and myocardium