Imprinting of Igf2/H19 andGnas: Reciprocal Imprinting and Chromosomal Insulation Model (Fig. 2)
Reciprocal imprinting of Igf2/H19 has been studied extensively. The imprinting of human DLK1/GTL2(mouse Dlk1/Gtl2) is similar to Igf2/H19imprinting. On the maternal allele, the IC is unmethylated. CTCF binds to the IC, which insulates enhancer activity from Igf2,only H19 is transcribed. On paternal allele, the IC is methylated, which prevents CTCF binding. The IC also spreads CpG methylation along the H19 promoter. Only Igf2is transcribed (sense and antisense). The Ihit1 transcript is located 20 kb upstream of H19 (Onyango et al. 2000). The imprinting status of Ihit1 has not been determined. Reciprocal imprinting in Gnas is more complex.Nesp and Xlas transcripts are reciprocally imprinted, while Gsα is transcribed from both parental alleles (Liu et al. 2000). A putative IC, 2 kb upstream ofGsα, is methylated on the maternal allele, which may act on the methylation of the maternal Xlas promoter.Nesp is transcribed from the unmethylated maternal promoter. On the paternal allele, the IC is unmethylated and so is theXlas promoter. Both Xlas and the IC (exon 1A) are transcribed (Liu et al. 2000). Antisense (Gnas-AS orNesp-AS) is also transcribed from the unmethylatedXlas promoter region (Li et al. 2000; Wroe et al. 2000), while the methylated Nesp promoter turns offNesp transcription. Enhancer activity and a chromosomal boundary have not yet been found.
