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Publication : Identification of an imprinting control region affecting the expression of all transcripts in the Gnas cluster.

First Author  Williamson CM Year  2006
Journal  Nat Genet Volume  38
Issue  3 Pages  350-5
PubMed ID  16462745 Mgi Jnum  J:106793
Mgi Id  MGI:3619611 Doi  10.1038/ng1731
Citation  Williamson CM, et al. (2006) Identification of an imprinting control region affecting the expression of all transcripts in the Gnas cluster. Nat Genet 38(3):350-5
abstractText  Genomic imprinting results in allele-specific silencing according to parental origin. Silencing is brought about by imprinting control regions (ICRs) that are differentially marked in gametogenesis. The group of imprinted transcripts in the mouse Gnas cluster (Nesp, Nespas, Gnasxl, Exon 1A and Gnas) provides a model for analyzing the mechanisms of imprint regulation. We previously identified an ICR that specifically regulates the tissue-specific imprinted expression of the Gnas gene. Here we identify a second ICR at the Gnas cluster. We show that a paternally derived targeted deletion of the germline differentially methylated region (DMR) associated with the antisense Nespas transcript unexpectedly affects both the expression of all transcripts in the cluster and methylation of two DMRs. Our results establish that the Nespas DMR is the principal ICR at the Gnas cluster and functions bidirectionally as a switch for modulating expression of the antagonistically acting genes Gnasxl and Gnas. Uniquely, the Nespas DMR acts on the downstream ICR at exon 1A to regulate tissue-specific imprinting of the Gnas gene.
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