Steve Hovland shovland at mindspring.com
Sun May 15 22:11:08 UTC 2005

Epigenetics refers to modifications in gene expression that are controlled 
by heritable but potentially reversible changes in DNA methylation and/or 
chromatin structure. DNA methylation is a post-replication process by which 
cytosine residues in CpG sequences are methylated, forming gene-specific 
methylation patterns. Housekeeping genes possess CpG-rich islands at the 
promoter region that are unmethylated in all cell types, whereas 
tissue-specific genes are methylated in all tissues except the tissue where 
the gene is expressed. These methylation patterns obviously correlate with 
gene expression. Further direct experiments proved that one of the most 
efficient gene-silencing mechanisms involves DNA methylation. Methylation 
patterns are established in the embryo by erasure of the gametic 
methylation patterns in the preimplantation embryo followed by global de 
novo methylation at the pregastrula stage, leaving CpG islands 
unmethylated. Finally, specific demethylation shapes the adult gene 
specific methylation patterns. Once a methylation pattern is established, 
it is clonally inherited using a maintenance methylasse that copies the 
methylation pattern on the parental DNA strand to the newly replicating 
strand. About 1% of the genes do not obey Mendel's genetic rules being 
expressed monoallelically in a parent-of-origin fashion. This phenomenon 
was called genomic imprinting and this subset of genes is imprinted by an 
epigenetic mechanism. The imprint must be established during gametogenesis, 
maintained during embryo development and erased in the primordial germ 
cells to set the stage for establishing a new imprint according to the 
gender of the embryo.

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