DNA Methylation in Mammalian and Non-Mammalian Organisms

Epigenetic reprogramming in mammalian cell differentiation, transdifferentiation and dedifferentiation.

“…Interestingly, while somatic cell reprogramming to iPSCs in many species has relied on over-expression of the conserved Yamanaka set of transcription factors, additional steps are likely needed here to achieve a true pluripotent state with competence for germ-line transmission [67,78]. Epigenetic modifications are evolutionary conserved but some variation exists between species in the modifying enzymes and binding protein homologues involved [9]. Overall, iPSC and ES cell technology have been mainly limited to rodents and humans.…”

“…Epigenetic modifications include the methylation states of cytosine residues of DNA and posttranslational methylation groups on the histone proteins associated with the DNA. Coregulator proteins with binding domains for these chemical groups may associate with these epigenetic marks and affect the activity of nearby genes [8,9]. The specific combination of epigenetic modifications may furthermore determine the conformation of the chromatin fibre into which the DNA and histones are packaged, and can thereby regulate the transcriptional potential of the underlying genes [4,10].…”

“…Specific epigenetic modifications and transcriptional profiles have been shown to have a dynamic potential for rapidly adapting to culture conditions [17,18] DNA methylation DNA methylation involves the addition of a methyl group to CpG sequences at the 5' position of the cytosine ring (5-methylcytosine; 5mC). This modification, which occurs in the DNA of most but not all eukaryotes, is catalysed by DNA methyltransferases (Dnmt) and is generally associated with gene repression [3,9,11]. The repression mechanisms can act through direct interference by the methyl group or involve a family of methyl binding proteins and associated complexes in vertebrates [9].…”

“…This modification, which occurs in the DNA of most but not all eukaryotes, is catalysed by DNA methyltransferases (Dnmt) and is generally associated with gene repression [3,9,11]. The repression mechanisms can act through direct interference by the methyl group or involve a family of methyl binding proteins and associated complexes in vertebrates [9]. DNA methylation can occur in two ways: de novo methylation relies on Dnmt3a and Dnmt3b enzymes that add new methyl groups to CpG sequences; whereas methylation maintenance requires Dnmt1 to restore methyl groups to hemi-methylated CpG sequences following DNA replication [3,12].…”