FIG. 7.

Summary of epigenetic modifications during the transition of human placental CTBs to STBs. (Top) The histone modification patterns in freshly prepared primary CTBs are diagrammed below the map. Prior to terminal STB differentiation, all the placental LCR HSs were already formed and the placental genes were expressed at trace levels, whereas hGH-N was totally inactive. Moderate levels of histone H3K4 dimethylation were observed at discrete regions, including HSV, the sites of the promoters of the placental genes, and the sites of the putative enhancers. Histone H3K4 trimethylation was also established at this point within the PGR regions. In contrast, only minimum levels of H3 acetylation were observed across the locus, and H4 acetylation was limited to HSV and at the placental-gene promoters. (Middle) After 4 days of culture, most of the CTBs fused to form a syncytium and the expression of the placental genes, especially hCS-A and hCS-B, was dramatically enhanced. Histone H3K4 di- and trimethylation patterns were well established, and the histone H3/H4 acetylation levels increased modestly at the LCR and at the cluster region in a block encompassing the four placental genes. (Bottom) In the full-term placental STBs, histone H3/H4 acetylation increased to maximum levels and the epigenetic patterns necessary for full activation of the placental genes were completed. The four placental genes are expressed at the highest levels, whereas hGH-N, lacking the epigenetic modifications, remains inactive in STBs.