title: Imprinted Igf2r silencing depends on continuous Airn lncRNA expression and is not restricted to a developmental window.
abstract: The imprinted Airn macro long non-coding (lnc) RNA is an established example of a cis-silencing lncRNA. Airn expression is necessary to initiate paternal-specific silencing of the Igf2r gene, which is followed by gain of a somatic DNA methylation imprint on the silent Igf2r promoter. However, the developmental requirements for Airn initiation of Igf2r silencing and the role of Airn or DNA methylation in maintaining stable Igf2r repression have not been investigated. Here, we use inducible systems to control Airn expression during mouse embryonic stem cell (ESC) differentiation. By turning Airn expression off during ESC differentiation, we show that continuous Airn expression is needed to maintain Igf2r silencing, but only until the paternal Igf2r promoter is methylated. By conditionally turning Airn expression on, we show that Airn initiation of Igf2r silencing is not limited to one developmental 'window of opportunity' and can be maintained in the absence of DNA methylation. Together, this study shows that Airn expression is both necessary and sufficient to silence Igf2r throughout ESC differentiation and that the somatic methylation imprint, although not required to initiate or maintain silencing, adds a secondary layer of repressive epigenetic information.
authors: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, 1090 Vienna, Austria.
authors: Federica
authors: F
authors: Santoro
authors: Daniela
authors: D
authors: Mayer
authors: Ruth M
authors: RM
authors: Klement
authors: Katarzyna E
authors: KE
authors: Warczok
authors: Alexey
authors: A
authors: Stukalov
authors: Denise P
authors: DP
authors: Barlow
authors: Florian M
authors: FM
authors: Pauler
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D020868:Gene Silencing / Q000502:physiology; D017930:Genes, Reporter; D018392:Genomic Imprinting / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D011401:Promoter Regions, Genetic / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000502:physiology; D017527:Receptor, IGF Type 2 / Q000235:genetics*; D013997:Time Factors; D014162:Transfection
chemical_list: C576864:Air non-coding RNA, mouse; D062085:RNA, Long Noncoding; D017527:Receptor, IGF Type 2