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. 2020 Jul 8;11:1178. doi: 10.3389/fimmu.2020.01178

Figure 1.

Figure 1

Extracellular and intracellular regulatory mechanisms of HLA-G expression. Variability in the HLA-G promoter region influences HLA-G expression by sensing and responding to the extracellular signals. Variations in the 3′ UTR region may modify mRNA stability or allow posttranscriptional regulation. HLA-G is not responsive to proinflammatory signals acting on the NF-κB pathway and to IFN-mediated stimulation. The HLA-G promoter region is unique among the HLA class I genes as it interacts with specific transcription factors activated by extracellular stimuli induced by hypoxia and heat shock, hormones such as glucocorticoids and progesterone, and cytokines including IL-10 and GM-CSF. HLA-G expression is posttranscriptionally regulated by genetic variations in the 3′ UTR, which contain several target sites for miRNAs and can bind specific RNA-binding proteins. These different regulations concur in the induction or inhibition of the expression of the HLA-G protein, which by alternative splicing of the mRNA can be produced in different isoforms: membrane-bound or soluble. 5′ URR, 5′ upstream regulatory region; 3′ UTR, 3′ untranslated region; CSF2RA, colony-stimulating factor 2 receptor subunit alpha; IL-10R, IL-10 receptor; IFNs, interferons; GR, glucocorticoid receptor; PR, progesterone receptor; HSP, heat shock protein, IRF-1, interferon regulatory factor 1; NF-κB, nuclear factor κ-light-chain-enhancer of activated B cells; RBP, RNA-binding proteins; miRNAs, microRNAs.