Identification of an imprinting control region affecting the expression of all transcripts in the Gnas cluster.
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.
Williamson
Christine M
CM
MRC Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.
Turner
Martin D
MD
Ball
Simon T
ST
Nottingham
Wade T
WT
Glenister
Peter
P
Fray
Martin
M
Tymowska-Lalanne
Zuzanna
Z
Plagge
Antonius
A
Powles-Glover
Nicola
N
Kelsey
Gavin
G
Maconochie
Mark
M
Peters
Jo
J
D000818:Animals; D002864:Chromogranins; D019175:DNA Methylation; D005091:Exons; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D018392:Genomic Imprinting; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D016372:RNA, Antisense / Q000235:genetics*; D022661:RNA, Untranslated / Q000235:genetics*; D017384:Sequence Deletion; D014158:Transcription, Genetic
D002864:Chromogranins; D016372:RNA, Antisense; D022661:RNA, Untranslated; C498642:Gnas protein, mouse; D019205:GTP-Binding Protein alpha Subunits, Gs