ArticleHuman molecular genetics2017
Overexpression of microRNAs from the Gtl2-Rian locus contributes to postnatal death in mice.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- The long non-coding RNA Meg3 mediates imprinted gene expression during stem cell differentiation.Nucleic acids research · 2024Article
- Maternal RNA transcription in Dlk1-Dio3 domain is critical for proper development of the mouse placental vasculature.Communications biology · 2024Article
- Expression patterns and DNA methylation profile ofAnimal biotechnology · 2023Article
- Balanced gene dosage control rather than parental origin underpins genomic imprinting.Nature communications · 2022Article
- Imprinted lncRNA Dio3os preprograms intergenerational brown fat development and obesity resistance.Nature communications · 2021Article
- Temple syndrome and Kagami-Ogata syndrome: clinical presentations, genotypes, models and mechanisms.Human molecular genetics · 2020Review
- Long noncoding RNA functionality in imprinted domain regulation.PLoS genetics · 2020Review
- Meg3-DMR, not the Meg3 gene, regulates imprinting of the Dlk1-Dio3 locus.Developmental biology · 2019Article
- Kinetics of the chromosome 14 microRNA cluster ortholog and its potential role during placental development in the pregnant mare.BMC genomics · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Dlk1-Dio3 imprinted domain functions in embryonic development but the roles of noncoding RNAs expressed from this domain remain unclear. We addressed this question by generating transgenic (TG) mice harbouring a BAC carrying IG-DMR (intergenic-differentially methylated region), Gtl2-DMR, Gtl2, Rtl1/Rtl1as, and part of Rian. High postnatal lethality (>85%) of the BAC-TG pups was observed in the maternally transmitted individuals (MAT-TG), but not following paternal transmission (PAT-TG). The DNA methylation status of IG-DMR and Gtl2-DMR in the BAC-allele was paternally imprinted similar to the genomic allele. The mRNA-Seq and miRNA-Seq analysis revealed marked expression changes in the MAT-TG, with 1,500 upregulated and 2,131 downregulated genes. The long noncoding RNAs and 12 miRNAs containing the BAC locus were markedly enhanced in the MAT-TG. We identified the 24 target genes of the overexpressed miRNAs and confirmed the downregulation in the MAT-TG. Notably, overexpression of mir770, mir493, and mir665 from Gtl2 in the MAT-TG embryos led to decreased expression of the 3 target genes, Col5a1, Pcgf2, and Clip2. Our results suggest that decreased expression of the 3 target genes concomitant with overexpression of the miRNAs within Gtl2 may be involved in the postnatal death in the MAT-TG. Because this imprinted domain is well conserved between mice and humans, the results of genetic and molecular analysis in mice hold important implications for related human disorders such as Temple syndrome.
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