Non‐classical transcriptional regulation of HLA‐G : an update

•  Introduction •  HLA‐G gene promoter region: regulatory sites and binding factors ‐  The atypical proximal promoter region of the HLA‐G gene among classical HLA class I genes ‐  Alternative regulatory elements within the HLA‐G gene promoter ‐  The locus control region ‐  cAMP response element/TPA response element ‐  Interferon‐stimulated response element ‐  Heat shock element ‐  Progesterone response element ‐  Leukaemia inhibitory factor target site ‐  Ras response elements‐  Sequence polymorphism within the HLA‐G gene promoter and 3′UT region ‐  Modulation of HLA‐G transcription by micro‐environmental factors with unidentified target sites ‐  Cytokines, growth factors, and hormones ‐  Hypoxia•  Chromatin remodelling at the HLA‐G gene locus •  Concluding remarksHuman leucocyte antigen‐G (HLA‐G) plays a key role in maternal–foetal tolerance and allotransplantation acceptance and is also implicated in tumour escape from the immune system. The modulation of HLA‐G expression can prove to be very important to therapeutic goals in some pregnancy complications, transplantation, cancer and possibly autoimmune diseases. In spite of substantial similarities with classical HLA ‐class I genes, HLA‐G is characterized by a restricted tissue‐specific expression in non‐pathological situations. HLA‐G expression is mainly controlled at the transcriptional level by a unique gene promoter when compared with classical HLA ‐class I genes, and at the post‐transcriptional level including alternative splicing, mRNA stability, translation and protein transport to the cell surface. We focus on the characteristics of the HLA‐G gene promoter and the factors which are involved in HLA‐G transcriptional modulation. They take part in epigenetic mechanisms that control key functions of the HLA‐G gene in the regulation of immune tolerance.