Variations in DNA methylation during mouse cell differentiation in vivo and in vitro.

Abstract

Mouse teratocarcinoma cells induced to differentiate in vitro undergo a massive (30%) demethylation of DNA. A similar undermethylation is also observed in the mouse extraembryonic membranes, the yolk sac and placenta. In both cases, the decrease in methyl moieties occurs at a large number of CpG sites spread out over the entire genome, as indicated by a restriction enzyme analysis of several mouse genes including dhfr, 13-major globin, and the H-2K gene family. In contrast to this, the embryo itself appears to undergo methylation de novo during early stages of embryogenesis. Thus, as opposed to somatic cells, events during early mouse development are associated with wide variations in the level of DNA methylation. Although these changes in DNA methylation seem to be an integral part of the differentiation process, its relation to specific gene expression is still unclear.

Epigenetics and the plasticity of differentiation in normal and cancer stem cells

“…Some cancers can be induced to differentiate by cytokines that regulate the differentiation of normal cells, whereas other cancers can differentiate in response to a variety of compounds including retinoic acid, dexamethasone, cytosine arabinoside and others (Sachs, 1978(Sachs, , 1987a(Sachs, , b, 1995(Sachs, , 1996Lotem and Sachs, 2002a, b). The differentiation of cancer cells is associated with epigenetic reprogramming of their DNA and/or chromatin (Razin et al, 1984;Cairns, 2001;Hong et al, 2001;Zhu et al, 2001;Di Croce et al, 2002). In some cases cancer cell differentiation can be induced by inhibitors of DNA methyltransferases (Dore et al, 1998) and/or histone deacetylases (Cameron et al, 1999;Wang et al, 1999;Marks et al, 2001;Munster et al, 2001).…”

Genome-wide demethylation during neural differentiation of P19 embryonal carcinoma cells

“…In mammals, DNA methylation mainly occurs at CpG dinucleotides, with approximately 60-90% of cytosines at these sites methylated (Razin et al 1984). CpG-rich DNA fragments, or CpG islands (Bird 1987), are preferentially located at the transcription start site of genes.…”

Isolation and characterization of a variant myoblast cell line that is temperature sensitive for differentiation.

“…Heterokaryon studies predict that such factors would be active even at late stages of differentiation (9), not just during the growth phase of the cell culture. It is also unlikely that the temperature-sensitive factor(s) mediates its activity by determining the methylation status of muscle-specific genes (44) (24) or by extracellular matrix interactions (33).…”