The differential expression of alternatively spliced transcripts and imprinting status of <i>MEG9</i> gene in cows

Zhang, Kun; Li, Dongjie; Wang, Mengnan; Wu, Guojiang; Shi, Yunjiao; Li, Shijie

doi:10.1111/age.12195

Cited by 4 publications

(3 citation statements)

References 24 publications

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“…In this study, aberrant transcription of MICO1 and MICO1OS were detected in some tissues of SCNT calves, but not in those conceived by artificial insemination, suggesting that improper imprinting of the locus may be responsible for the deviant expression. Yet, among all the SCNT bovine tissues with aberrant transcription of MICO1 and MICO1OS , monoallelic expression of GTL2 , MEG9 , and DIO3 was maintained—as reported by others (Wang et al, ; Zhang et al, )—indicating that regulation of MICO1 is independent of the mechanisms that control GTL2 , MEG9 , or DIO3 expression Indeed, similar DNA hypermethylation of the genes within this imprinted locus was observed between the comparative tissues of artificial‐insemination and SCNT calves with normal or abnormal MICO1 production. Thus, DNA methylation does not appear to directly or indirectly affect allelic transcription of MICO1 and MICO1OS .…”

Section: Discussionsupporting

confidence: 70%

Aberrant expression ofMICO1andMICO1OSin deceased somatic cell nuclear transfer calves

Wang

Yang

et al. 2017

Mol Reprod Dev

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Incomplete reprogramming of a donor nucleus following somatic cell nuclear transfer (SCNT) results in aberrant expression of developmentally important genes, and is the primary source of the phenotypic abnormalities observed in cloned animals. Expression of non-coding RNAs in the murine Dlk1-Dio3 imprinted domain was previously shown to correlate with the pluripotency of mouse induced pluripotent stem cells. In this study, we examined the transcription of the bovine orthologs from this locus, MICO1 (Maternal intergenic circadian oscillating 1) and MICO1OS (MICO1 opposite strand), in tissues from artificially inseminated and SCNT calves that died during the perinatal period. A single-nucleotide polymorphism (SNP), a T-to-C transition, was used to analyze the allelic transcription of MICO1. Our results indicate monoallelic expression of the MICO1C allele among the six analyzed tissues (heart, liver, spleen, lung, kidney, and brain) of artificially inseminated calves, indicating that this gene locus may be imprinted in bovine. Conversely, we observed variable allelic transcription of MICO1 in SCNT calves. We asked if DNA methylation regulated the monoallelic expression of MICO1 and MICO1OS by evaluating the methylation levels of six regions within or around this locus in tissues with normal or aberrant MICO1 transcription; all of the samples from either artificially inseminated or SCNT calves exhibited hypermethylation, implying that DNA methylation may not be involved in regulating its monoallelic expression. Furthermore, three imprinted genes (GTL2, MEG9, and DIO3) nearby MICO1 showed monoallelic expression in SCNT calves with aberrant MICO1 transcription, indicating that not all of the genes in the bovine DLK1-DIO3 domain are mis-regulated.

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Section: Discussionsupporting

confidence: 70%

Aberrant expression ofMICO1andMICO1OSin deceased somatic cell nuclear transfer calves

Wang

Yang

et al. 2017

Mol Reprod Dev

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“…We further validated the array data by qRT-PCR from etoposide and another inducer of genotoxic stress, ionizing radiation, and both increased MEG9 expression in HUVECs (Fig 1C). Similarly, we observed a dose-responsive induction of MEG9 in human microvascular endothelial cells (HMVECs) (Fig 1D).MEG9 is a highly conserved lncRNA across mammals, presenting several isoforms in humans, mouse and cattle[29,36]. MEG9 is highly enriched in human and mouse brain and other highly vascularized tissues such as lung, liver and heart (Fig 2A-B).…”

supporting

confidence: 57%

“…MEG9 is a highly conserved lncRNA across mammals, presenting several isoforms in humans, mouse and cattle [29, 36]. MEG9 is highly enriched in human and mouse brain and other highly vascularized tissues such as lung, liver and heart (Fig 2A-B).…”

Section: Resultsmentioning

confidence: 99%

DNA damage-induced lncRNA MEG9 impacts angiogenesis

Fraile-Bethencourt

Khou

Wilson

et al. 2022

Preprint

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Endothelial cells are highly responsive to environmental changes that allow them to adapt to intrinsic and extrinsic stimuli and switch their transcriptome accordingly to go back to vascular homeostasis. Our previous data demonstrated that small non-coding-RNAs respond quickly to genotoxic stressors and determined endothelial cell fate and DNA damage response. To further understand the contribution of non-coding-RNAs, we profiled differentially expressed long non-coding RNAs in response to genotoxic stress and compared them to pro-angiogenic growth factor signaling. We identified the Maternally expressed gene 9 (MEG9) as a cytoprotective lncRNA in the endothelium. Gain and Loss-of-function studies indicate that MEG9 prevents endothelial cells from cell death, suggesting that MEG9 responses to genotoxic stress can be an adaptive and protective mechanism. Consistent with this phenotype, the knockdown of MEG9 decreases growth factor-dependent angiogenesis in a 3D fibrin gel angiogenesis assay. Deletion of the MEG9 ortholog, Mirg, in mice results in increased vascular leak in Matrigel plugs and a sex and age-dependent decrease in platelets. Mechanistically, we observed that both MEG9 knockdown in vitro and Mirg-deleted mice in vivo activated common pathways, including apoptosis, clotting, and inflammation. Indeed, the proinflammatory adhesion molecule ICAM1 was significantly increased in human and mouse endothelial cells in a MEG9-dependent manner, supporting the increased vascular permeability observed on MEG9 deficient cells. Taken together, our findings illustrate how genotoxic stress responses through dynamic modulation of lncRNAs, such as MEG9, trigger adaptive mechanisms to maintain endothelial function, while loss of these molecules contributes to maladaptive responses and endothelial cell dysfunction.

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An imprinted long noncoding RNA located between genes Meg8 and Meg9 in the cattle Dlk1-Dio3 domain

Zhang¹,

Zhao

Wang³

et al. 2016

Genetica

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The Dlk1-Dio3 imprinted domain is located on the cattle chromosome 21 and contains three paternally expressed protein-coding genes and a number of maternally expressed short or long noncoding RNA genes. We have previously obtained two maternally expressed long noncoding RNA genes, Meg8 and Meg9, from the cattle. In this study, we identified a novel noncoding RNA located between Meg8 and Meg9 known as LINC24061 according to the GENCODE annotated bibliography. Two alternatively spliced transcripts (LINC24061-v1 and LINC24061-v2) were obtained using RT-PCR and RACE, and the expression pattern of LINC24061-v1 and LINC24061-v2 was shown to be tissue-specific. The LINC24061-v1 splice variant was expressed in only three types of tissues: heart, kidney and muscle; in contrast, LINC24061-v2 was expressed in all eight tissues examined, including heart, liver, spleen, lung, kidney, skeletal muscle, subcutaneous fat, and brain of adult cattle. The allele-specific expression of LINC24061 was identified based on a single nucleotide polymorphism (SNP) in exon 2 of LINC24061. The results showed that LINC24061 exhibited monoallelic expression in all the examined cattle tissues.

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The differential expression of alternatively spliced transcripts and imprinting status of MEG9 gene in cows

Cited by 4 publications

References 24 publications

Aberrant expression ofMICO1andMICO1OSin deceased somatic cell nuclear transfer calves

Aberrant expression ofMICO1andMICO1OSin deceased somatic cell nuclear transfer calves

DNA damage-induced lncRNA MEG9 impacts angiogenesis

An imprinted long noncoding RNA located between genes Meg8 and Meg9 in the cattle Dlk1-Dio3 domain

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