IMPRINTING MECHANISMS

A number of recent studies have provided new insights into mechanisms that regulate genomic imprinting in the mammalian genome. Regions of a llele-specific differential methylation (DMRs) are present in all impr inted genes examined. Differential methylation is erased in germ cells at an early stage of their development, and germ-line-specific methyl ation imprints in DMRs are reestablished around the time of birth. Aft er fertilization, differential methylation is retained in core DMRs de spite genome-wide demethylation and de novo methylation during preimpl antation and early postimplantation stages. Direct repeats near CC-ric h DMRs may be involved in the establishment and maintenance of allele- specific methylation patterns. Imprinted genes tend to be clustered; o ne important component of clustering is enhancer competition, whereby promoters of linked imprinted genes compete for access to enhancers. R egional organization and spreading of the epigenotype during developme nt is also important and depends on DMRs and imprinting centers. The m echanism of cis spreading of DNA methylation is not known, but precede nt is provided by the Xist RNA, which results in X chromosome inactiva tion in cis. Reading of the somatic imprints could be carried out by t ranscription factors that are sensitive to methylation, or by methyl-c ytosine-binding proteins that are involved in transcriptional repressi on through chromatin remodeling.