Genetic analysis of genomic methylation patterns in plants and mammals

While it is now accepted that methylation of cytosine residues plays a role in various epigenetic phenomena in mammals and flowering plants, the involvement of methylation patterns in the regulation of normal development has remained a controversial and essentially untested issue in the 20 years since such a role was first proposed. Antisense suppression of a DNA methyltransferase in Arabidopsis and characterization of methylation-defective mutants of Arabidopsis have shown that perturbations of methylation patterns disrupt the development of plants, and targeted mutation of the murine gene that encodes the one known from of DNA methyltransferase has shown that methylation is required for cellular differentiation, genomic imprinting, and X chromosome inactivation in mammals. Ectopic expression of homeotic genes and homeotic transformations of floral organs in methylation-defective plants suggest that (in plants and perhaps mammals) heritable methylation patterns reinforce and may have supplanted heritable gene control mediated by chromosomal proteins of the Polycomb and trithorax groups. It is also possible that the developmental abnormalities are the result of ectopic gene expression caused by activation of transcription from nearby parasitic sequence elements that are normally repressed by methylation. Application of modern methods of genetic analysis promises to give definite answers to long-standing questions as to the roles and significance of genomic methylation patterns in normal development and genome defense.