Dr. Alexander Meissner discusses the roles of epigenetic mechanisms in stem cells and development.
Cytosine methylation in mammals is an epigenetic modification that is largely restricted to CpG dinucleotides and serves multiple critical functions including stable repression of target promoters, maintaining genomic integrity, establishing parent-specific imprinting patterns, and silencing endogenous retrotransposon activity. In somatic tissues, CpG methylation exhibits global patterns based on relative CpG density: it is unmethylated in localized CpG islands at housekeeping or developmental promoters, and hypermethylated at non-regulatory CpGs distributed elsewhere in the genome.
This landscape is relatively static across all somatic tissues that have been examined to date on a genome scale, where the majority of methylated CpGs are pre-established and inherited through cell divisions. Generally, only a small fraction of CpGs switch their methylation levels as part of an orchestrated regulatory event. By contrast, DNA methylation is much more dynamic during mouse germ-cell and pre-implantation development. Recent insights gained through genome-scale mapping of DNA methylation and histone modifications in stem cells and development will be presented.