The <i>Dlk1</i> and <i>Gtl2</i> genes are linked and reciprocally imprinted

Schmidt, Jennifer V.; Matteson, Paul G.; Jones, Beverly K.; Guan, Xiao; Tilghman, Shirley M.

doi:10.1101/gad.14.16.1997

Cited by 272 publications

(27 citation statements)

References 34 publications

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“…Maternally expressed gene 3 (MEG3), also known as gene trap locus 2 (Gtl2), is located at chromosome 14q32.3 within Dlk1-Dio3 locus [24,25]. Knockdown of MEG3 has been found to potentiate insulin resistance and impair glucose homeostasis in diet-induced obese mice [26].…”

Section: Meg3mentioning

confidence: 99%

Regulation of Oxidative Stress by Long Non-Coding RNAs in Vascular Complications of Diabetes

Chu

Tsai

et al. 2022

Life

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Diabetes mellitus is a well-known metabolic disorder with numerous complications, such as macrovascular diseases (e.g., coronary heart disease, diabetic cardiomyopathy, stroke, and peripheral vascular disease), microvascular diseases (e.g., diabetic nephropathy, retinopathy, and diabetic cataract), and neuropathy. Multiple contributing factors are implicated in these complications, and the accumulation of oxidative stress is one of the critical ones. Several lines of evidence have suggested that oxidative stress may induce epigenetic modifications that eventually contribute to diabetic vascular complications. As one kind of epigenetic regulator involved in various disorders, non-coding RNAs have received great attention over the past few years. Non-coding RNAs can be roughly divided into short (such as microRNAs; ~21–25 nucleotides) or long non-coding RNAs (lncRNAs; >200 nucleotides). In this review, we briefly discussed the research regarding the roles of various lncRNAs, such as MALAT1, MEG3, GAS5, SNHG16, CASC2, HOTAIR, in the development of diabetic vascular complications in response to the stimulation of oxidative stress.

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Section: Meg3mentioning

confidence: 99%

Regulation of Oxidative Stress by Long Non-Coding RNAs in Vascular Complications of Diabetes

Chu

Tsai

et al. 2022

Life

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“…In addition to PEG10 and H19 , there are several imprinted regions that are accompanied by novel acquired genes. In the Delta like non-canonical Notch ligand 1 ( DLK1 )-Iodothyronine deiodinase 3 ( DI O 3 ) region, a large insertion comprising MEG3, Retrotransposon GAG-like 1 ( RTL1 ) /PEG11, antiRTL1/antiPEG11, and MEG8/ RNA imprinted and accumulated in nucleus ( RIAN ) and MEG9/ microRNA-containing gene ( MIRG ) occurred in association with the emergence of an intergenic (IG) -DMR between DLK1 and MEG3 in eutherians ( Kobayashi et al, 2000 ; Miyoshi et al, 2000 ; Schmidt et al, 2000 ; Wylie et al, 2000 ; Charlier et al, 2001 ; Edwards et al, 2008 ). Thus, they are eutherian-specific genes: RTL1/PEG11 is a protein coding gene while the other maternally expressed non-coding RNAs include a cluster of siRNA and/or snoRNAs ( Charlier et al, 2001 ; Cavaillé et al, 2002 ).…”

Section: Novel Functions Provided By Newly Acquired Imprinted Genes I...mentioning

confidence: 99%

The Evolutionary Advantage in Mammals of the Complementary Monoallelic Expression Mechanism of Genomic Imprinting and Its Emergence From a Defense Against the Insertion Into the Host Genome

Kaneko-Ishino

Ishino

2022

Front. Genet.

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In viviparous mammals, genomic imprinting regulates parent-of-origin-specific monoallelic expression of paternally and maternally expressed imprinted genes (PEGs and MEGs) in a region-specific manner. It plays an essential role in mammalian development: aberrant imprinting regulation causes a variety of developmental defects, including fetal, neonatal, and postnatal lethality as well as growth abnormalities. Mechanistically, PEGs and MEGs are reciprocally regulated by DNA methylation of germ-line differentially methylated regions (gDMRs), thereby exhibiting eliciting complementary expression from parental genomes. The fact that most gDMR sequences are derived from insertion events provides strong support for the claim that genomic imprinting emerged as a host defense mechanism against the insertion in the genome. Recent studies on the molecular mechanisms concerning how the DNA methylation marks on the gDMRs are established in gametes and maintained in the pre- and postimplantation periods have further revealed the close relationship between genomic imprinting and invading DNA, such as retroviruses and LTR retrotransposons. In the presence of gDMRs, the monoallelic expression of PEGs and MEGs confers an apparent advantage by the functional compensation that takes place between the two parental genomes. Thus, it is likely that genomic imprinting is a consequence of an evolutionary trade-off for improved survival. In addition, novel genes were introduced into the mammalian genome via this same surprising and complex process as imprinted genes, such as the genes acquired from retroviruses as well as those that were duplicated by retropositioning. Importantly, these genes play essential/important roles in the current eutherian developmental system, such as that in the placenta and/or brain. Thus, genomic imprinting has played a critically important role in the evolutionary emergence of mammals, not only by providing a means to escape from the adverse effects of invading DNA with sequences corresponding to the gDMRs, but also by the acquisition of novel functions in development, growth and behavior via the mechanism of complementary monoallelic expression.

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“…[1][2][3][4][5][6][7][8][9][10][11] It is coded by a maternally imprinted, paternally expressed gene localized on chromosome 14 in human and chromosome 12 in mouse. 2,[12][13][14] DLK1 exists in different forms. The full-length protein is composed of six epidermal growth factor (EGF)-like tandem repeats that constitute the major part of the extracellular domain (ECD), a transmembrane domain (TMD), and a short intracellular domain (ICD).…”

Section: Introductionmentioning

confidence: 99%

“… 1 – 11 It is coded by a maternally imprinted, paternally expressed gene localized on chromosome 14 in human and chromosome 12 in mouse. 2 , 12 – 14 …”

Section: Introductionmentioning

confidence: 99%

Emerging Roles of DLK1 in the Stem Cell Niche and Cancer Stemness

Grassi

Pietras

2021

J Histochem Cytochem.

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DLK1 is a maternally imprinted, paternally expressed gene coding for the transmembrane protein Delta-like homologue 1 (DLK1), a non-canonical NOTCH ligand with well-described roles during development, and tumor-supportive functions in several aggressive cancer forms. Here, we review the many functions of DLK1 as a regulator of stem cell pools and tissue differentiation in tissues such as brain, muscle, and liver. Furthermore, we review recent evidence supporting roles for DLK1 in the maintenance of aggressive stem cell characteristics of tumor cells, specifically focusing on central nervous system tumors, neuroblastoma, and hepatocellular carcinoma. We discuss NOTCH -dependent as well as NOTCH-independent functions of DLK1, and focus particularly on the complex pattern of DLK1 expression and cleavage that is finely regulated from a spatial and temporal perspective. Progress in recent years suggest differential functions of extracellular, soluble DLK1 as a paracrine stem cell niche-secreted factor, and has revealed a role for the intracellular domain of DLK1 in cell signaling and tumor stemness. A better understanding of DLK1 regulation and signaling may enable therapeutic targeting of cancer stemness by interfering with DLK1 release and/or intracellular signaling.

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The Dlk1 and Gtl2 genes are linked and reciprocally imprinted

Cited by 272 publications

References 34 publications

Regulation of Oxidative Stress by Long Non-Coding RNAs in Vascular Complications of Diabetes

Regulation of Oxidative Stress by Long Non-Coding RNAs in Vascular Complications of Diabetes

The Evolutionary Advantage in Mammals of the Complementary Monoallelic Expression Mechanism of Genomic Imprinting and Its Emergence From a Defense Against the Insertion Into the Host Genome

Emerging Roles of DLK1 in the Stem Cell Niche and Cancer Stemness

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