RESUMEN
DNA methylation is crucial for mammalian development, and DNA methylation is always in the dynamic status during preimplantation mouse embryos development. The effects of 5-AZA-CdR on the development of preimplantation mouse embryos were evaluated. Preimplantation mouse embryos created by in vitro fertilization were cultured continuously in 5-AZA-CdR (0.2, 1.0, or 5.0 μmol/L). Fertilized oocytes exposed to CZB containing 5-AZA-CdR at the pronuclear stage were unable to form morulae (0.2 and 1.0 μmol/L) or 4-cell embryos (5.0 μmol/L), while 2-cell stage embryos exposed to 5-AZA-CdR developed into uncompacted 8-cell (0.2 and 1.0 μmol/L) or 3/4-cell (5.0 μmol/L) stage embryos. The rate of morula formation was significantly lower in 4-cell embryos cultured in 5-AZA-CdR (1.0 or 5.0 μmol/L) than that in control embryos (P < 0.05). These data indicate that 5-AZA-CdR inhibits the development of mouse preimplantation embryos. Apoptosis, DNA methylation, and transcriptional activity were analyzed to determine the reason for these developmental defects. An aunexin V-PI assay revealed that high doses of 5-AZA-CdR led to apoptosis. Compared to the controls, DNA methylation was significantly reduced in uncompacted 8-cell embryos and morulae (p < 0.05) in a dose- dependent manner, whereas no significant change was detected in 2-or 4-cell embryos (P > 0.05). The observed changes in transcriptional activity, determined by measuring the incorporation of BrUTP, were similar to the observed alterations in DNA methylation. Therefore, the developmental defects induced by 5-AZA-CdR appear to bc mediated by alterations in DNA methylation and transcriptional activity in preimplantation mouse embryos.
RESUMEN
Epigenetic modifications, including DNA methylation, histone modifications, RNA epigenetics and nucleosome remodeling, are important for gene transcription, but such modifications do not change the coding sequence of the gene. Although these events are heritable, they are potentially reversible, thus opening up opportunities for the therapy of cancer. So epigenetic modifications have been thrusted into the forefront of new drug discoveries. Current knowledge suggests that the agents that intervene epigenetics by "turning back on" silenced genes may represent a significant advancement in treating many forms of cancer. In this review, we summarized the research progress of epigenetic gene regulation and the proteins which could read epigenetic codes. And the relationship between epigenetics and cancer was discussed comprehensively.