1. Nat. Rev. Endocrinol. doi:10.1038/nrendo.2016.138
Figure 2 The imprinted domains of chromosome 11p15 that are implicated in Silver–Russell syndrome
Figure 2 | The imprinted domains of chromosome 11p15 that are implicated in Silver–Russell syndrome. a | Representation of the 11p15 region, showing both centromeric and telomeric domains. Only the imprinted genes that are implicated in the pathophysiology of Silver–Russell syndrome are represented. Blue boxes indicate paternally expressed genes (the growth promoter IGF2 and the long noncoding RNA (lncRNA) KCNQ1OT1). Red boxes indicate maternally expressed genes (the growth inhibitor CDKN1C, the ion channel KCNQ1 and the noncoding RNA H19). Ovals indicate differentially methylated regions (DMRs). Dark grey ovals indicate methylated DMRs. Beige ovals indicate unmethylated DMRs. b | Structure of the H19/IGF2 IG-DMR (intergenic differentially methylated region). This DMR contains short repetitive blocks of sequence and harbours seven binding sites for the zinc finger protein CTCF (green circles). Multiple enhancer elements (grey hexagons) distal to H19 are shared between H19 and IGF2, and are able to increase expression of either. Binding of CTCF to the unmethylated maternal DMR blocks interactions between the IGF2 promoter and enhancers downstream of H19, which results in maternal H19 expression. Conversely, methylation of ICR1 on the paternal allele prevents CTCF binding, enabling interaction between the IGF2 promoter and distal enhancers, and thus paternal IGF2 expression162,163. Beige triangles indicate unmethylated CTCF binding sites. Dark grey triangles indicate methylated CTCF binding sites.
Wakeling, E. L. et al. (2016) Diagnosis and management of Silver–Russell syndrome: first international consensus statement
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