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Imprinted gene expression at the Dlk1-Dio3 cluster is controlled by both maternal and paternal IG-DMRs in a tissue-specific fashion.

ABSTRACT: Imprinting at the Dlk1-Dio3 cluster is controlled by the IG-DMR, an imprinting control region differentially methylated between maternal and paternal chromosomes. The maternal IG-DMR is essential for imprinting control, functioning as a cis enhancer element. Meanwhile, DNA methylation at the paternal IG-DMR is thought to prevent enhancer activity. To explore whether suppression of enhancer activity at the methylated IG-DMR requires the transcriptional repressor TRIM28, we analyzed Trim28chatwo embryos and performed epistatic experiments with IG-DMR deletion mutants. We found that while TRIM28 regulates the enhancer properties of the paternal IG-DMR, it also controls imprinting through other mechanisms. Additionally, we found that the paternal IG-DMR, previously deemed dispensable for imprinting, is required in certain tissues, demonstrating that imprinting is regulated in a tissue-specific manner. Using ChRO-seq to analyze nascent transcription, we show that different tissues have a distinctive regulatory landscape at the Dlk1-Dio3 cluster, providing insight into potential mechanisms of tissue-specific imprinting control. ChRO-seq identified 30 novel transcribed regulatory elements, including a candidate regulatory region that depends on the paternal IG-DMR. Together, our findings challenge the model that Dlk1-Dio3 imprinting is regulated through a single mechanism and demonstrate that different tissues use distinct strategies for imprinting control.

ORGANISM(S): Mus musculus

PROVIDER: GSE119882 | GEO | 2019/02/28

REPOSITORIES: GEO

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A bipartite element with allele-specific functions safeguards DNA methylation imprints at the Dlk1-Dio3 locus [4C-seq]

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Loss of imprinting at the CTCF binding sites in the DLK1-DIO3 domain reactivates microRNA expression in acute promyelocytic leukaemia

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Silencing of maternally expressed RNAs in Dlk1-Dio3 domain is critical for embryonic development

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Meg3 non-coding RNA expression controls imprinting by preventing transcriptional up-regulation in cis

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