title: Imprinted silencing of Slc22a2 and Slc22a3 does not need transcriptional overlap between Igf2r and Air.
abstract: Silencing of the paternal allele of three imprinted genes (Igf2r, Slc22a2 and Slc22a3) requires cis expression of the Air RNA that overlaps the promoter of one of them (Igf2r). Air is a non-coding RNA whose mode of action is unknown. We tested the role of the Igf2r promoter and the role of transcriptional overlap between Igf2r and Air in silencing in this cluster. We analyzed imprinted expression in mice in which the Igf2r promoter is replaced by a thymidine kinase promoter that preserves a transcription overlap with Air, and in mice with a deleted Igf2r promoter that lack any transcriptional overlap with Air. Imprinted silencing of Air, Slc22a2 and Slc22a3 is maintained by the replacement promoter and also in the absence of transcriptional overlap with Air. These results exclude a role for the Igf2r promoter and for transcriptional overlap between Igf2r and Air in silencing Air, Slc22a2 and Slc22a3. Although these results do not completely exclude a role for a double-stranded RNA silencing mechanism, they do allow the possibility that the Air RNA has intrinsic cis silencing properties.
authors.affiliation: Department of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Sleutels
authors.forename: Grace
authors.initials: G
authors.lastname: Tjon
authors.forename: Thomas
authors.initials: T
authors.lastname: Ludwig
authors.forename: Denise P
authors.initials: DP
authors.lastname: Barlow
mesh_terms: D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002678:Chimera; D019175:DNA Methylation; D020868:Gene Silencing; D018392:Genomic Imprinting / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D027701:Organic Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D000075102:Organic Cation Transporter 2; D011401:Promoter Regions, Genetic; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism*; D017527:Receptor, IGF Type 2 / Q000235:genetics*; D017384:Sequence Deletion; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism; D000099254:Organic Cation Transporter 3
chemical_list: D002352:Carrier Proteins; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; D022661:RNA, Untranslated; D017527:Receptor, IGF Type 2; D000099254:Organic Cation Transporter 3; C491012:Slc22a2 protein, mouse