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 remarks Human 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.