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

Abstract

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.

Analysis of the intracellular traffic of IgG in the context of Down syndrome (trisomy 21)

“…It will be of interest to test whether the AICD fragment regulates the expression of FcRn. Points that merit further consideration are (1) whether the observed FCGRT - APP gene expression correlation extends to “inter-individual” comparisons involving various cell types and tissues from multiple donors, and (2) additional regulatory mechanisms that may impact FCGRT and FcRn expression in trisomic cells 61 , 62 .…”

Nursing Informatics and Epigenetics

“…25 Studies have linked DNAm to gene expression and disease processes, because DNAm can cause the gene to not be expressed (see Figure 3), and the removal of a methyl group can cause the gene to be expressed. [27][28][29] DNAm can be measured and compared using discrete methylation differential data. If comparing two cells, one from a disease process such as cancer and the other a control, the methylation of the exact same CpG site can be measured to determine the methylation level, which is reported as being hyper-methylated or hypo-methylated in the diseased cell.…”

In Translation: FcRn across the Therapeutic Spectrum

“…Polymorphisms in intron 1 of FCGRT , which encodes for FcRn, affects FcRn abundance, mAb distribution between central and peripheral compartments, and the efficiency of intravenous Ig (IVIg) therapy [ 55 , 113 , 114 ]. Methylation-sensitive transcription factors Zbtb7a and Sp1 as well as the microRNAs hsa-miR-3181 and hsa-miR-3136-3p have been found to affect FCGRT expression [ 115 , 116 ]. Others have found that FcRn expression responds to immunological stimuli, with detailed investigations showing upregulation by tumor necrosis factor (TNF)-α through NF-κB and downregulation by interferon (IFN)-γ through JAK/STAT-1 [ 117 , 118 ].…”