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. Author manuscript; available in PMC: 2010 Mar 30.
Published in final edited form as: Trends Genet. 2007 Apr 18;23(6):284–292. doi: 10.1016/j.tig.2007.03.018

Figure 1.

Figure 1

Genomic organization of three imprinted mouse clusters containing ncRNAs tested for their silencing function. Only a few genes in each cluster show widespread imprinted expression in extra-embryonic, embryonic and adult tissues, and most genes in a cluster show imprinted expression only in extra-embryonic tissues; thus, the expression pattern in this cell lineage is illustrated. (a) The paternally imprinted Igf2 cluster spans ~80 kb and contains the 2.5-kb H19 ncRNA [68]. Igf2 and H19 show ubiquitous imprinted expression, whereas Ins2 shows imprinted expression only in the extra-embryonic visceral yolk sac. Imprinted expression operates through the ICE, which is itself regulated by a DNA methylation imprint. On the maternal chromosome (pink), the CTCF protein binds to the unmethylated maternal ICE and forms an insulator that blocks the interaction of downstream enhancers to the Igf2 and Ins2 promoters but allows their interaction with the H19 ncRNA promoter. On the paternal chromosome (blue), the DNA methylation imprint blocks CTCF binding. Thus, the enhancers interact with the Igf2 and Ins2 promoters [66]. (b) The maternally imprinted Kcnq1 cluster spans ~800 kb and contains the Kcnq1ot1 ncRNA [16]. The Kcnq1ot1 promoter lies in an antisense orientation in the ICE in intron 10 of the Kcnq1 gene; its full length is unknown, as is whether it overlaps the Kcnq1 promoter. Cdkn1c and the Kcnq1ot1 ncRNA show ubiquitous imprinted expression, whereas the remainder show only limited imprinted expression in the early embryo or in extra-embryonic tissues. Imprinted expression operates through the ICE that contains the Kcnq1ot1 ncRNA promoter. On the paternal chromosome, the Kcnq1ot1 ncRNA is expressed and eight imprinted mRNA promoters are repressed. On the maternal chromosome, the methylated ICE represses the Kcnq1ot1 ncRNA promoter, enabling expression of the eight imprinted mRNAs only on this chromosome [4]. In this cluster, two genes (Nap1/4 and Phemx) show expression from both alleles, although expression of the paternal is less than that of the maternal allele [42]. (c) The maternally imprinted Igf2r cluster spans ~500 kb and contains the 108-kb Air ncRNA [67]. The Air promoter lies in antisense orientation in the ICE in Igf2r intron 2. In this cluster, Igf2r and the Air ncRNA show ubiquitous imprinted expression, whereas the remainder of the genes in the cluster show imprinted expression only in extra-embryonic tissues. Imprinted expression operates through the ICE that contains the Air ncRNA promoter. On the paternal chromosome, the Air ncRNA is expressed and three imprinted mRNA promoters are repressed. On the maternal chromosome, the methylated ICE represses the Air ncRNA promoter, enabling expression of the three imprinted mRNAs only on this chromosome [5]. Gene loci (not to scale) for which the gene name is not given in full are abbreviated as follows: Asc, Ascl2; Cd8, Cd81; Cdk, Cdkn1c; Nap, Nap1/4; Osb, Osbpl5; Phe, Phemx; Phl, Phlda2; Slc, Slc22a18; Trp, Trpm5; Tss, Tssc4.