Figure 4. Epigenetic mechanisms operative in mammalian cells.

In addition to genetically inheritable mechanisms that coordinate cell proliferation, growth and differentiation, several epigenetic mechanisms are operative in mammalian cells to ensure the fidelity of gene expression through generations. DNA methylation is a well established mechanism that epigenetically controls the silencing of many developmental genes, often irreversibly, to ensure lineage commitment. DNA methylation is also an important mechanism for silencing tumor suppressor genes during tumor progression. Histone modifications are another established parameter of epigenetic control. Over 60 histone modifications regulate and fine-tune gene regulation under various biological conditions. Recently, RNA mediated gene silencing is gaining attention as another epigenetic mechanism. The most notable example is the inactivation of one copy of X chromosome in females. One of the two copies of active X-chromosomes (labeled here as Xa) is inactivated (labeled here as Xi) by Xist RNA. Recently, micro-RNA mediated down-regulation of gene expression is being extensively investigated. miRs are typically transcribed by RNA ploymerase II as precursor-miRs, that are processed by enzymes Drosha and Dicer to generate 22 nt long mature miRs. Mature miRs recognize the seed sequence in target mRNA and lead to their degradation, thus negatively regulating gene expression. A novel epigenetic mechanism that is emerging is the mitotic retention of phenotypic proteins on target gene loci to ensure lineage commitment and maintenance in progeny cells. Depicted here is the mitotic localization of Runx2 transcription factor to nucleolar organizing regions (NORs) were the ribosomal RNA genes reside, as well as to the RNA Pol II regulated genes that are involved in cell cycle control and lineage commitment.