Is ZFP57 binding to H19/IGF2 :IG-DMR affected in Silver-Russell syndrome?
Abstract
Loss of paternal methylation (LOM) of the H19/IGF2 intergenic differentially methylated region (H19/IGF2:IG-DMR) causes alteration of H19/IGF2 imprinting and Silver-Russell syndrome (SRS). Recently, internal deletions of the H19/IGF2:IG-DMR have been associated with LOM and SRS when present on the paternal chromosome. In contrast, previously described deletions, most of which cause gain of methylation (GOM) and Beckwith-Wiedemann syndrome (BWS) on maternal transmission, were consistently associated with normal methylation and phenotype if paternally inherited. The presence of several target sites (ZTSs) and three demonstrated binding regions (BRs) for the imprinting factor ZFP57 in the H19/IGF2:IG-DMR suggest the involvement of this factor in the maintenance of methylation of this locus. By comparing the extension of the H19/IGF2:IG-DMR deletions with the binding profile of ZFP57, we propose that the effect of the deletions on DNA methylation and clinical phenotype is dependent on their interference with ZFP57 binding. Indeed, deletions strongly affecting a ZFP57 BR result in LOM and SRS, while deletions preserving a significant number of ZFPs in each BR do not alter methylation and are associated with normal phenotype. The gen...Continue Reading
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Beckwith-Wiedemann syndrome
Beckwith-Wiedemann syndrome is an imprinting disorder characterized by overgrowth, congenital malformations and predisposition to tumors. Discover the latest research on Beckwith-Wiedemann Syndrome here.