PRDM1 blocking peptide

The loss of PRDM1 expression is common in extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT), but the role of promoter methylation in silencing PRDM1 expression remains unclear. Hence, we performed pyrosequencing analysis to evaluate the promoter methylation of PRDM1 gene in vivo and in vitro, to analyze the association between methylation and its expression, and to assess cellular effects of PRDM1 reexpression. The promoter hypermethylation of PRDM1 gene was detected in 11 of 25 EN-NK/T-NT cases (44.0%) and NK92 and NKL cells. The promoter hypermethylation of PRDM1 was significantly correlated with PRDM1 expression in vivo and in vitro, predominantly contributing to the loss of PRDM1 expression compared with genetic deletion and aberrant expression of miR-223 in EN-NK/T-NT. PRDM1 expression was significantly restored by demethylation treatment, which induced cell proliferation suppression, cell cycle arrest, and apoptosis increase. We also found that PRDM1 reexpression could downregulate the expression of Ets-1, T-bet, granzyme B, and c-myc. Our findings demonstrated that the promoter hypermethylation of PRDM1 harbored a predominant role in the downregulation of PRDM1 expression, significantly affecting the biological behavior of tumor cells in EN-NK/T-NT.

In many animal embryos, a specific gene expression pattern is established along the animal-vegetal axis soon after zygotic transcription begins. In the embryo of the ascidian Ciona intestinalis, soon after the division that separates animal and vegetal hemispheres into distinct blastomeres, maternal Gata.a and beta-catenin activate specific genes in the animal and vegetal blastomeres, respectively. On the basis of these initial distinct gene expression patterns, gene regulatory networks promote animal cells to become ectodermal tissues and vegetal cells to become endomesodermal tissues and a part of the nerve cord. In the vegetal hemisphere, beta-catenin directly activates Foxd, an essential transcription factor gene for specifying endomesodermal fates. In the present study, we found that Foxd also represses the expression of genes that are activated specifically in the animal hemisphere, including Dmrt1, Prdm1-r.a (Bz1), Prdm1-r.b (Bz2), and Otx. A reporter assay showed that Dmrt1 expression was directly repressed by Foxd, and a chromatin immunoprecipitation assay showed that Foxd was bound to the upstream regions of Dmrt1, Prdm1-r.a, Prdm1-r.b, and Otx. Thus, Foxd has a dual function of activating specific gene expression in the vegetal hemisphere and of repressing the expression of genes that are normally expressed in the animal hemisphere. This dual function stabilizes the initial patterning along the animal-vegetal axis by beta-catenin and Gata.a.