The &lt;i&gt;H19&lt;/i&gt; gene: regulation and function of a non-coding RNA

Gabory, Anne; Ripoche, Marie‐Anne; Yoshimizu, Tomomi; Dandolo, Luisa

doi:10.1159/000090831

Cited by 207 publications

(157 citation statements)

References 125 publications

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“…In H19 Δ3 mice, expression of the maternal Igf2 allele is 25% that of the paternal allele in wild-type mice, and is only observed in mesoderm derived tissues (skeletal muscle, tongue, diaphragm and heart) (Ripoche et al, 1997;Yoshimizu et al, 2008). The reactivation of the maternal Igf2 allele in both H19 targeted models is most probably due to a cis effect of an altered chromatin structure rather than to the lack of the H19 RNA (for a review, see Gabory et al, 2006). Different studies have lead to proposals of a role for the H19 RNA itself.…”

Section: δ3mentioning

confidence: 99%

H19acts as a trans regulator of the imprinted gene network controlling growth in mice

et al. 2009

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The imprinted H19 gene produces a non-coding RNA of unknown function. Mice lacking H19 show an overgrowth phenotype, due to a cis effect of the H19 locus on the adjacent Igf2 gene. To explore the function of the RNA itself, we produced transgenic mice overexpressing H19. We observed postnatal growth reduction in two independent transgenic lines and detected a decrease of Igf2 expression in embryos. An extensive analysis of several other genes from the newly described imprinted gene network (IGN) was performed in both loss-and gain-of-function animals. We found that H19 deletion leads to the upregulation of several genes of the IGN. This overexpression is restored to the wild-type level by transgenic expression of H19. We therefore propose that the H19 gene participates as a trans regulator in the fine-tuning of this IGN in the mouse embryo. This is the first in vivo evidence of a functional role for the H19 RNA. Our results also bring further experimental evidence for the existence of the IGN and open new perspectives in the comprehension of the role of genomic imprinting in embryonic growth and in human imprinting pathologies.

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Section: δ3mentioning

confidence: 99%

H19acts as a trans regulator of the imprinted gene network controlling growth in mice

et al. 2009

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“…Generally, based on the position of the lncRNA relative to the neighbouring protein‐coding genes in the genome, lncRNAs can be divided into five categories, namely: sense, antisense, bidirectional, intronic and intergenic 7. Although lncRNAs have been investigated less often than miRNAs, a number of lncRNAs have been functionally characterized, such as HOTAIR 8, 9, Xist 10 and H19 11, 12, 13. Recent reports have shown that lncRNAs are involved in the regulatory roles in diverse processes, such as imprinting, X‐inactivation and development.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the miRNA–mRNA–lncRNA networks in ER+ and ER− breast cancer cell lines

Guo

Jiang

et al. 2015

J Cellular Molecular Medi

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Recently, rapid advances in bioinformatics analysis have expanded our understanding of the transcriptome to a genome‐wide level. miRNA–mRNA–lncRNA interactions have been shown to play critical regulatory role in cancer biology. In this study, we discussed the use of an integrated systematic approach to explore new facets of the oestrogen receptor (ER)‐regulated transcriptome. The identification of RNAs that are related to the expression status of the ER may be useful in clinical therapy and prognosis. We used a network modelling strategy. First, microarray expression profiling of mRNA, lncRNA and miRNA was performed in MCF‐7 (ER‐positive) and MDA‐MB‐231 cells (ER‐ negative). A co‐expression network was then built using co‐expression relationships of the differentially expressed mRNAs and lncRNAs. Finally, the selected miRNA–mRNA network was added to the network. The key miRNA–mRNA–lncRNA interaction can be inferred from the network. The mRNA and non‐coding RNA expression profiles of the cells with different ER phenotypes were distinct. Among the aberrantly expressed miRNAs, the expression levels of miR‐19a‐3p, miR‐19b‐3p and miR‐130a‐3p were much lower in the MCF‐7 cells, whereas that of miR‐148b‐3p was much higher. In a cluster of miR‐17‐92, the expression levels of six of seven miRNAs were lower in the MCF‐7 cells, in addition to miR‐20b in the miR‐106a‐363 cluster. However, the levels of all the miRNAs in the miR‐106a‐25 cluster were higher in the MCF‐7 cells. In the co‐expression networking, CD74 and FMNL2 gene which is involved in the immune response and metastasis, respectively, had a stronger correlation with ER. Among the aberrantly expressed lncRNAs, lncRNA‐DLEU1 was highly expressed in the MCF‐7 cells. A statistical analysis revealed that there was a co‐expression relationship between ESR1 and lncRNA‐DLEU1. In addition, miR‐19a and lncRNA‐DLEU1 are both located on the human chromosome 13q. We speculate that miR‐19a might be co‐expressed with lncRNA‐DLEU1 to co‐regulate the expression of ESR1, which influences the occurrence and development of breast cancer cells with different levels of ER expression. Our findings reveal that the status of ER is mainly due to the differences in the mRNA and ncRNA profile between the breast cancer cell lines, and highlight the importance of studying the miRNA–mRNA–lncRNA interactions to completely illustrate the intricate transcriptome.

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“…One of the most abundant noncoding RNA transcripts found in our TGC RNA-Seq data set was H19 [Fragments Per Kilobase of transcript per Million reads mapped (FPKM) = 24,368], a tumor-suppresor noncoding RNA gene (44)(45)(46)(47). As H19 is not only the first imprinted noncoding transcript discovered, but also is the known precursor for miR-675 (48, 49), we analyzed the miRNA composition of the TGCs by deep sequencing.…”

Section: Tgcs Mksmentioning

confidence: 99%

Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells

Sher

Stetina

Bell

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Throughout the plant and animal kingdoms specific cell types become polyploid, increasing their DNA content to attain a large cell size. In mammals, megakaryocytes (MKs) become polyploid before fragmenting into platelets. The mammalian trophoblast giant cells (TGCs) exploit their size to form a barrier between the maternal and embryonic tissues. The mechanism of polyploidization has been investigated extensively in Drosophila , in which a modified cell cycle—the endocycle, consisting solely of alternating S and gap phases—produces polyploid tissues. During S phase in the Drosophila endocycle, heterochromatin and specific euchromatic regions are underreplicated and reduced in copy number. Here we investigate the properties of polyploidization in murine MKs and TGCs. We induced differentiation of primary MKs and directly microdissected TGCs from embryonic day 9.5 implantation sites. The copy number across the genome was analyzed by array-based comparative genome hybridization. In striking contrast to Drosophila , the genome was uniformly and integrally duplicated in both MKs and TGCs. This was true even for heterochromatic regions analyzed by quantitative PCR. Underreplication of specific regions in polyploid cells is proposed to be due to a slower S phase, resulting from low expression of S-phase genes, causing failure to duplicate late replicating genomic intervals. We defined the transcriptome of TGCs and found robust expression of S-phase genes. Similarly, S-phase gene expression is not repressed in MKs, providing an explanation for the distinct endoreplication parameters compared with Drosophila . Consistent with TGCs endocycling rather than undergoing endomitosis, they have low expression of M-phase genes.

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The <i>H19</i> gene: regulation and function of a non-coding RNA

Cited by 207 publications

References 125 publications

H19acts as a trans regulator of the imprinted gene network controlling growth in mice

H19acts as a trans regulator of the imprinted gene network controlling growth in mice

Analysis of the miRNA–mRNA–lncRNA networks in ER+ and ER− breast cancer cell lines

Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells

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