Developmental regulation of somatic imprints

Abstract

Genomic imprinting is an epigenetic phenomenon guiding the allele-specific marking of parental alleles. Genes regulated by imprinting are only or preferentially expressed from a single allele during development and in the adult, and the transcriptional activity of each allele is dictated by its parental origin. Consequently, active and repressed alleles of imprinted genes are marked by activating and repressive histone marks, respectively. Whether these marks are implicated in the germline imprints distinguishing maternal and paternal alleles at fertilization or indeed in the mitotic inheritance of the two transcriptional states is currently unknown. The only epigenetic modification which is known to fulfill these roles is DNA methylation. Most but not all imprinted genes are marked by regions of allele-specific DNA methylation termed differentially methylated regions (DMRs). Whereas some DMRs, the gametic DMRs, are directly inherited from the mature gametes at fertilization, others, the somatic DMRs, are only acquired in postimplantation embryos. Although all somatic imprints are thought to emerge as a consequence of the cis-activity of a nearby gametic imprint, the molecular mechanisms guiding the de novo methylation at somatic DMRs are not fully understood. Here we review the known characteristics of gametic and somatic DMRs, with an emphasis on the factors implicated in the initiation and maintenance of these epigenetic marks. The analysis of somatic DMRs offers the opportunity to study the mechanism of de novo DNA methylation outside the context of the germline and as such might help to elucidate common mechanisms implicated in epigenetic silencing during development and differentiation. Moreover, studies on genes directly silenced by somatic DMRs may be informative in understanding the significance of controlling gene dosage in the adult.