RT Journal A1 Constância, Miguel A1 Pickard, Benjamin A1 Kelsey, Gavin A1 Reik, Wolf T1 Imprinting Mechanisms JF Genome Research JO Genome Research YR 1998 FD September 01 VO 8 IS 9 SP 881 OP 900 DO 10.1101/gr.8.9.881 UL http://genome.cshlp.org/content/8/9/881.abstract AB A number of recent studies have provided new insights into mechanisms that regulate genomic imprinting in the mammalian genome. Regions of allele-specific differential methylation (DMRs) are present in all imprinted genes examined. Differential methylation is erased in germ cells at an early stage of their development, and germ-line-specific methylation imprints in DMRs are reestablished around the time of birth. After fertilization, differential methylation is retained in core DMRs despite genome-wide demethylation and de novo methylation during preimplantation and early postimplantation stages. Direct repeats near CG-rich DMRs may be involved in the establishment and maintenance of allele-specific methylation patterns. Imprinted genes tend to be clustered; one important component of clustering is enhancer competition, whereby promoters of linked imprinted genes compete for access to enhancers. Regional organization and spreading of the epigenotype during development is also important and depends on DMRs and imprinting centers. The mechanism of cis spreading of DNA methylation is not known, but precedent is provided by theXist RNA, which results in X chromosome inactivation incis. Reading of the somatic imprints could be carried out by transcription factors that are sensitive to methylation, or by methyl–cytosine-binding proteins that are involved in transcriptional repression through chromatin remodeling.