A bipartite element with allele-specific functions safeguards DNA methylation imprints at the Dlk1-Dio3 locus.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsAronson, Boaz E
Glenn, Rachel A
Dawlaty, Meelad M
MetadataShow full item record
AbstractLoss of imprinting (LOI) results in severe developmental defects, but the mechanisms preventing LOI remain incompletely understood. Here, we dissect the functional components of the imprinting control region of the essential Dlk1-Dio3 locus (called IG-DMR) in pluripotent stem cells. We demonstrate that the IG-DMR consists of two antagonistic elements: a paternally methylated CpG island that prevents recruitment of TET dioxygenases and a maternally unmethylated non-canonical enhancer that ensures expression of the Gtl2 lncRNA by counteracting de novo DNA methyltransferases. Genetic or epigenetic editing of these elements leads to distinct LOI phenotypes with characteristic alternations of allele-specific gene expression, DNA methylation, and 3D chromatin topology. Although repression of the Gtl2 promoter results in dysregulated imprinting, the stability of LOI phenotypes depends on the IG-DMR, suggesting a functional hierarchy. These findings establish the IG-DMR as a bipartite control element that maintains imprinting by allele-specific restriction of the DNA (de)methylation machinery.
CitationjDev Cell. 2021 Nov 22;56(22):3052-3065.e5. doi: 10.1016/j.devcel.2021.10.004. Epub 2021 Oct 27.
AffiliationBRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
PublisherElsevier (Cell Press)
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International
- A tandem repeat array in IG-DMR is essential for imprinting of paternal allele at the Dlk1-Dio3 domain during embryonic development.
- Authors: Saito T, Hara S, Kato T, Tamano M, Muramatsu A, Asahara H, Takada S
- Issue date: 2018 Sep 15
- The paternally imprinted DLK1-GTL2 locus is differentially methylated in embryonal and alveolar rhabdomyosarcomas.
- Authors: Schneider G, Bowser MJ, Shin DM, Barr FG, Ratajczak MZ
- Issue date: 2014 Jan
- Meg3-DMR, not the Meg3 gene, regulates imprinting of the Dlk1-Dio3 locus.
- Authors: Zhu W, Botticelli EM, Kery RE, Mao Y, Wang X, Yang A, Wang X, Zhou J, Zhang X, Soberman RJ, Klibanski A, Zhou Y
- Issue date: 2019 Nov 1
- Involvement of PGC7 and UHRF1 in the regulation of DNA methylation of the IG-DMR in the imprinted Dlk1-Dio3 locus.
- Authors: Yu M, Liu Y, Han Z, Du W, Chen B, Zhang L, Xue H, Zhang Z, Guo Z
- Issue date: 2022 Jul 25
- Epigenome editing reveals core DNA methylation for imprinting control in the Dlk1-Dio3 imprinted domain.
- Authors: Kojima S, Shiochi N, Sato K, Yamaura M, Ito T, Yamamura N, Goto N, Odamoto M, Kobayashi S, Kimura T, Sekita Y
- Issue date: 2022 May 20