Imprinting and the Initiation of Gene Silencing in the Germ Line

of loss of function of paternal and maternal allele-specific genes, respectively (Dittrich et al., 1996). Many imprinted genes here, including SNRPN, are unmethylated on the paternal chromosome but methylated on the maternal chromosome. Mutations within the SNRPN exon 1 region cause PWS, and those that occur further upstream and affect certain RNA (BD) transcripts cause AS. The imprinting center (IC) responsible for initiating the epigenetic switch in the germ line is therefore pro-Inheritance of genes in active or repressed states re-posed to consist of an imprinter (BD transcripts) and a quires appropriate chromosomal modifications and DNA switch initiation site (SNSIS) located in the SNRPN exon methylation. Imprinting of a determined state into the 1 region (Dittrich et al., 1996; see later). chromatin structure therefore constitutes a memory of In mice, transgenic experiments have provided a strin-all developmental decisions taken within individual cells. gent test for putative control elements. A 300 kb Igf2r Genomic or gametic imprinting is however a unique YAC transgene was demonstrated to undergo appro-manifestation of such epigenetic inheritance in which priate imprinting with expression after maternal inheri-expression of certain genes is governed by their parental tance only (Wutz et al., 1997). Deletion of an intronic origin, from generation to generation. Some of these CpG island, which is differentially methylated in the fe-genes show expression after paternal inheritance while male germ line, abolished imprinting of the YAC clone others are expressed only when inherited from the ma-and resulted in biallelic Igf2r expression. However, small ternal germ line. The most striking feature of imprinted transgenes containing this intronic region alone have so genes therefore is that the active and inactive parental far failed to display imprinting. The key question remains alleles coexist within individual cells. Over 20 imprinted and that is how methylation of the intronic CpG island genes have so far been identified. Parental genomes are initiated in the germ line. Similarly, a 130 kb YAC trans-functionally nonequivalent during development because gene with the H19 and Igf2 genes displayed appropriate of the differential expression of imprinted genes. imprinting of both of them (Ainscough et al., 1997); the To accomplish monoallelic expression of imprinted two genes demonstrate mutually exclusive expression genes, these loci are subject to germ line–specific epige-in cis. There are a number of putative control regions netic modifications, which are propagated subsequently located on the YAC, amongst which there is one near from sperm and egg to …