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In tumor tissues, alterations of gene expression caused by aberrant epigenetic modifications confer phenotypic diversity on malignant cells. Although 3-deazaneplanocin A (DZNep) has been shown to reactivate tumor suppressor genes in several cancer cells, it remains unclear whether DZNep attenuates the malignant phenotypes of oral squamous cell carcinoma (OSCC) cells. In this study, we investigated the effect of DZNep on the expression of genes related to aggressive phenotypes, such as epithelial–mesenchymal transition, in OSCC cells. We found that DZNep reduced the cellular levels of polycomb group proteins (EZH2, SUZ12, BMI1, and RING1A) and the associated trimethylation of Lys27 on histone H3 and monoubiquitination of Lys119 on histone H2A in the poorly differentiated OSCC cell line SAS. Immunocytochemical staining demonstrated that DZNep induced the reorganization of filamentous actin and the membrane localization of E-cadherin associated with cell–cell adhesions. We also found an inhibitory effect of DZNep on cell proliferation using a WST assay. Finally, quantitative RT-PCR analysis demonstrated that genes involved in the aggressive phenotypes (TWIST2, EGFR, ACTA2, TGFB1, WNT5B, and APLIN) were down-regulated, whereas epithelial phenotype genes (CDH1, CLDN4, IVL, and TGM1) were up-regulated in SAS cells treated with DZNep. Collectively, our findings suggest that DZNep reverses the aggressive characteristics of OSCC cells through the dynamic regulation of epithelial plasticity via the reprogramming of gene expression patterns. [ABSTRACT FROM AUTHOR]

Highlights: [•] Nspc1 participates in maintaining P19 embryonal carcinoma cell’s pluripotency. [•] The epigenetics repressor Nspc1 positively regulates Oct4–Nanog–Sox2 axis. [•] Nspc1 directly binds and activates Oct4 promoter in a dose dependent manner. [•] The activation effect of Nspc1 is dependent on the RA response element. [ABSTRACT FROM AUTHOR]

Abstract: SUZ12 is a Polycomb group protein that forms Polycomb repressive complexes (PRC2/3) together with EED and histone methyltransferase EZH2. Although the essential role of SUZ12 in regulating the activity of the PRC2/3 complexes has been demonstrated, additional function of this protein was suggested. Here, we show that SUZ12 interacts with WD-repeat protein MEP50 in vitro and in vivo. We show that the MEP50 binds histone H2A selectively among core histones, and mediates transcriptional repression of protein arginine methyltransferase PRMT5, which is known to methylate H2A and H4. These results suggest that SUZ12 might have a role in transcriptional regulation through physical interaction with MEP50 that can be an adaptor between PRMT5 and its substrate H2A. [Copyright &y& Elsevier]

Abstract: Gene expression, differentiation and the specialized function of various cell types are controlled epigenetically by post-translational histone modifications. These modifications establish a “histone code” that is recognized by various regulatory proteins, thereby creating a stable pattern of gene expression. The focus of this review is to discuss how the chromatin modifications regulate immunoglobulin gene rearrangement and B cell differentiation. [Copyright &y& Elsevier]