Induction of class II MHC antigen expression on the murine placenta by 5-azacytidine correlates with fetal abortion

Methylation of Class IItrans-Activator Promoter IV: A Novel Mechanism of MHC Class II Gene Control

“…Some studies have examined the affect of chronic exposure to 5AC on class II expression and embryo viability in mice and rats (54 -56), and the results have varied. Although Athanassakis-Vassiliadis et al (54) found that 5AC induced class II expression in the placenta and that this correlated with fetal loss, Gustafsson et al (55) and Yuan et al (56) found no evidence of increased class II expression on trophoblast cells after 5AC treatment. However, in none of these studies was the methylation status of the CIITA gene examined either before or after 5AC treatment, so it is unclear whether CIITA re-expression (which is necessary for MHC class II gene expression) was achieved.…”

Repression of MHC class II gene transcription in trophoblast cells by novel single-stranded DNA binding proteins

“…Did repression of class II gene transcription in trophoblast cells mediated by IAαNRE BPs arise during evolution to prevent fetal rejection, thereby maintaining reproduction and perpetuation of the species? The importance of class II gene regulation to fetal maintenance is suggested by the studies of Athanassakis-Vassiliadis et al (1990. Induction of class II antigen expression on fetal placental cells by 5-azacytidine was shown to correlate with fetal abortion (Athanassakis-Vassiliadis et al, 1989).…”

“…Trophoblast cells do not constitutively express class II antigens, and expression cannot be induced by IFN-γ or TNF-α (Chatterjee-Hasrouni and Lala, 1981;Hunt et al, 1990a,b;Salter-Cid and Flajnik, 1995). The importance of class II gene regulation in fetal maintenance is suggested by studies demonstrating that aberrant expression of class II antigens on mouse or human placental tissue strongly correlated with abortion (Athanassakis-Vassiliadis et al, 1990.…”

Constitutive intracellular expression of human leukocyte antigen (HLA)-DO and HLA-DR but not HLA-DM in trophoblast cells

“…The murine system allowed to easily address the question of whether the mRNA transcript of classic class II genes possess the transmembrane region or whether there exists a different tailless isoform, which, as in the case of HLA-G5, facilitates secretion. The murine trophoblast experimental model expresses only the classic H-2A molecules because the H-2E genes were previously found to be methylated [27]. By use of a specific primer for the transmembrane region of the H-2A␣ gene, RT-PCR experiments detected the presence of this region in the untreated as well as the IFN-␥-treated TROPHO-1 cells.…”

“…Methylation of class II gene or class II transactivator promoter IV, however, does not mediate such process because class II can be de novo induced by interferon-␥ (IFN-␥), a fact that is correlated to fetal abortion [27][28][29]. Furthermore, other studies have suggested that silencing of the class II transactivator (CIITA) transcription in trophoblasts involves an epigenetic mechanism rather than promoter type IV methylation [30].…”