PMC:521203 / 19765-21262 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/521203","sourcedb":"PMC","sourceid":"521203","source_url":"https://www.ncbi.nlm.nih.gov/pmc/521203","text":"Two reagents have been widely used for the alteration of the levels of epigenetic modification of somatic cells. Trichostatin A (TSA) and 5-aza-deoxy-cytadine (5-aza-dC) have been found to increase histone acetylation and decrease DNA methylation, respectively. These changes have been associated with increases of gene expression. Recently, we conducted studies in which the pre-existing epigenetic marks in donor cells were reduced by these drugs [49]. We found that global epigenetic marks in donor cells can be modified by treatment with TSA or 5-aza-dC. Unfortunately, treating donor cells with 5-aza-dC reduced blastocyst formation of cloned embryos. Previously, Jones et al. [50] and Zhou et al. [51] treated bovine fetal fibroblast cells and mouse stem cells with much higher doses of 5-aza-C (1 or 5 μm) and also found that blastocyst development of cloned embryos were reduced. The consensus from these studies [49-51] suggests that lowering the levels of DNA methylation in donor cells does not always improve development of cloned embryos. At high concentrations, 5-aza-dC may have been cytotoxic to the donor cells. Additionally, prolonged treatment at a lower concentration, as was the case in our study, may have caused severe hypo-methylation, and resulted in disrupted expression of essential genes important for embryo development. Therefore, further experiments are required to test the effects of lower concentrations and shorter durations of 5-aza-dC treatment on donor cells.","tracks":[]}