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| Open AccessEpigenetic regulation of Neuregulin 1 promotes breast cancer progression associated to hyperglycemia
Despite hyperglycemia has been associated to breast cancer, the underlying mechanisms are not completely understood. Here, the authors show that epigenetic regulation of Nrg1 gene during hyperglycemia promotes breast cancer development.
- Changhu Lee
- , Min Kim
- & Jiyoung Park
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Article
| Open AccessParent-of-Origin inference for biobanks
Studies on parent-of-origin effects have been limited in terms of sample size due to lack of parental genomes or known genealogies. Here, the authors develop a method to infer the parent-of-origin of an individual alleles in biobank-scale datasets, without requiring parental genomes or prior knowledge of genealogy, allowing discovery of parent-of-origin effects with an unprecedented sample size.
- Robin J. Hofmeister
- , Simone Rubinacci
- & Olivier Delaneau
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| Open AccessImprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation
Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) is associated with epigenetic alterations. Here the authors assess DNA methylation in detail in multiple female and male mouse iPSC lines generated with different protocols and find that defects depend on the sex of donor cells and can be partially mitigated by Vitamin C.
- Maria Arez
- , Melanie Eckersley-Maslin
- & Simão Teixeira da Rocha
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| Open AccessPaternal imprinting of dosage-effect defective1 contributes to seed weight xenia in maize
Xenia effects describe the genetic contribution of pollen to seed phenotypes. Here the authors show that paternal imprinting of Ded1 contributes to the xenia effect in maize by setting the pace of endosperm development.
- Dawei Dai
- , Janaki S. Mudunkothge
- & A. Mark Settles
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| Open AccessBalanced gene dosage control rather than parental origin underpins genomic imprinting
Here the authors investigate whether for imprinted genes the parent-of-origin of the expressed allele or rather appropriate gene dosage is more important for normal development. Using the differentially methylated region of Dlk1-Dio3 gene involved in imprinting, they show that correct parent-of-origin imprinting pattern is secondary to balanced gene dosage.
- Ariella Weinberg-Shukron
- , Raz Ben-Yair
- & Yonatan Stelzer
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| Open AccessThe microRNA cluster C19MC confers differentiation potential into trophoblast lineages upon human pluripotent stem cells
Little is known about the epigenetic mechanisms of the first cell fate commitment in humans. Here, the authors show that activation of the miRNA cluster C19MC confers differentiation potential into trophoblast lineages on human embryonic stem cells.
- Norio Kobayashi
- , Hiroaki Okae
- & Takahiro Arima
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| Open AccessEpigenetic changes induced by in utero dietary challenge result in phenotypic variability in successive generations of mice
Here the authors show that a high-fat diet in pregnant mice can release silencing of the imprinted Dlk1 locus in multiple generations of offspring. They found that this occurs via changes in microRNA expression at the locus of interest, as well as transcriptional changes across the genome, in the developing oocytes.
- Mathew Van de Pette
- , Andrew Dimond
- & Amanda G. Fisher
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| Open AccessIdentifying regulators of parental imprinting by CRISPR/Cas9 screening in haploid human embryonic stem cells
Genetic imprinting ensures monoallelic gene expression critical for normal embryonic development. Here the authors take advantage of human haploid parthenogenic embryonic stem cells lacking paternal alleles to identify, by genome-wide screening, factors involved in the regulation of imprinted genes.
- Shiran Bar
- , Dan Vershkov
- & Nissim Benvenisty
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Article
| Open AccessLarge parental differences in chromatin organization in pancreatic beta cell line explaining diabetes susceptibility effects
A SNP distant from the human insulin (INS) gene near the KRTAP5-6 gene confers increased susceptibility to type 2 diabetes when present on the paternal allele while decreased susceptibility when on the maternal allele. Here the authors show that long-range contacts between the INS locus and the KRTAP5-6 gene locus distinguish paternal and maternal alleles.
- Xing Jian
- & Gary Felsenfeld
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| Open AccessGenomic imprinting in mouse blastocysts is predominantly associated with H3K27me3
In most mammals, imprinted genes contain epigenetic marks that differ in each parental genome and control their parent-of-origin-specific expression. Here, the authors map imprinted genes in mouse preimplantation embryos and find that imprinted gene expression in blastocysts is mainly dependent on Polycomb-mediated H3K27me3-associated gene silencing.
- Laura Santini
- , Florian Halbritter
- & Martin Leeb
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Article
| Open AccessMaternal DNMT3A-dependent de novo methylation of the paternal genome inhibits gene expression in the early embryo
The paternal genome in mice undergoes widespread DNA methylation loss post-fertilization. Here, the authors apply allele-specific analysis of WGBS data to show that a number of genomic regions are simultaneously de novo methylated on the paternal genome dependent on maternal DNMT3A activity, which induces transcriptional silencing of this allele in the early embryo.
- Julien Richard Albert
- , Wan Kin Au Yeung
- & Matthew Lorincz
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Article
| Open AccessLoss of H3K27me3 imprinting in the Sfmbt2 miRNA cluster causes enlargement of cloned mouse placentas
Somatic cell nuclear transfer (SCNT) frequently results in abnormal placenta development in cloned mice. Here the authors show that loss of histone methylation (H3K27me3) imprinting in clustered Sfmbt2 miRNAs contributes to SCNT placenta defect.
- Kimiko Inoue
- , Narumi Ogonuki
- & Atsuo Ogura
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Article
| Open AccessImprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development
How the imprinted Cdkn1c locus regulates corticogenesis is unclear. Here, the authors dissect the level of cell-autonomy of imprinted Cdkn1c gene function in mouse corticogenesis and identify this as regulating radial glial progenitor cell and projection neuron survival.
- Susanne Laukoter
- , Robert Beattie
- & Simon Hippenmeyer
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| Open AccessEvolution of imprinting via lineage-specific insertion of retroviral promoters
Although many species-specific imprinted genes have been identified, how the evolutionary switch from biallelic to imprinted expression occurs is still unknown. Here authors find that lineage-specific ERVs active as oocyte promoters can induce de novo DNA methylation at gDMRs and imprinting.
- Aaron B. Bogutz
- , Julie Brind’Amour
- & Louis Lefebvre
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Article
| Open AccessTET3 prevents terminal differentiation of adult NSCs by a non-catalytic action at Snrpn
The potential role of TET proteins in adult neurogenesis is unknown. In this study, authors show that TET3 is essentially required for the maintenance of the NSC pool in the adult subventricular zone niche by preventing premature differentiation of NSCs, via direct binding and repression of the paternal transcribed allele of the imprinted gene Snrpn
- Raquel Montalbán-Loro
- , Anna Lozano-Ureña
- & Sacri R. Ferrón
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| Open AccessIntergenerational inheritance of high fat diet-induced cardiac lipotoxicity in Drosophila
Animal studies have shown that the nutritional status of parents can predispose the offspring to obesity and obesity-related diseases. Here the authors show that cardiac dysfunction induced by a high-fat diet persists for two generations in Drosophila, and that targeted expression of ATGL/bmm in the offspring, as well as inhibition of H3K27 trimethylation, is cardioprotective.
- Maria Clara Guida
- , Ryan Tyge Birse
- & Rolf Bodmer
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| Open AccessLincRNA H19 protects from dietary obesity by constraining expression of monoallelic genes in brown fat
Brown adipose tissue (BAT) thermogenesis counteracts obesity and promotes metabolic health. The role of long non-coding RNAs (lncRNAs) in the regulation of this process is not well understood. Here the authors identify a maternally expressed lncRNA, H19, that increases BAT oxidative metabolism and energy expenditure.
- Elena Schmidt
- , Ines Dhaouadi
- & Jan-Wilhelm Kornfeld
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Article
| Open AccessNucleoporin 107, 62 and 153 mediate Kcnq1ot1 imprinted domain regulation in extraembryonic endoderm stem cells
Genomic imprinting restricts transcription to predominantly one parental allele. Here the authors perform a screen for epigenetic factors involved in paternal allelic silencing at the Kcnq1ot1 imprinted domain in mouse extraembryonic endoderm stem cells and characterize a role for specific nucleoporins in mediating Kcnq1ot1 imprinted regulation.
- Saqib S. Sachani
- , Lauren S. Landschoot
- & Mellissa R. W. Mann
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| Open AccessParental haplotype-specific single-cell transcriptomics reveal incomplete epigenetic reprogramming in human female germ cells
In mammalian female germ cells, parent-specific epigenetic marks are erased and the X chromosome reactivated before entry into meiosis. Here, by combining parental haplotype reconstruction with single-cell transcriptomics of human female embryonic germ cells, the authors demonstrate that epigenetic reprogramming occurs in a heterogeneous fashion and during a broad time window up to week 14.
- Ábel Vértesy
- , Wibowo Arindrarto
- & Susana M. Chuva de Sousa Lopes
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| Open AccessCopy number rather than epigenetic alterations are the major dictator of imprinted methylation in tumors
Altered genomic imprinting is frequently reported in cancer. Here, the authors analyze copy number and methylation in cancer cell lines and primary tumors to show that imprinted methylation profiles represent the accumulation of copy number alteration, rather than epigenetic alterations.
- Alex Martin-Trujillo
- , Enrique Vidal
- & David Monk
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Article
| Open AccessEpigenetic and genetic components of height regulation
Adult height has a strong genetic component and is highly heritable. Here the authors whole-genome sequence 8,453 Icelanders and find novel parent-of-origin derived associations in IGF2-H19 and DLK1-MEG3.
- Stefania Benonisdottir
- , Asmundur Oddsson
- & Kari Stefansson
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| Open AccessDifferential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis
Selective biallelic expression of certain genes through genomic imprinting are known to play a role in controlling neurogenesis in the adult mammalian brain. Here the authors investigate the role of imprinting in the dosage control of Igf2 and its relevance for the function of IGF2 as a neurogenic regulator in the mouse brain.
- S. R. Ferrón
- , E. J. Radford
- & A. C. Ferguson-Smith
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Article
| Open AccessDppa3 expression is critical for generation of fully reprogrammed iPS cells and maintenance of Dlk1-Dio3 imprinting
Reprogramming of mouse somatic cells into iPSCs often generates pre-iPSCs, low-grade iPSCs that show abnormal Dlk1-Dio3 imprinting, and fully reprogrammed, high-grade iPSCs. Here, the authors show that germ-cell marker Dppa3 enhances reprogramming kinetics, critical for the maintenance of Dlk1-Dio3 imprinting and generation of fully reprogrammed iPSCs.
- Xingbo Xu
- , Lukasz Smorag
- & D. V. Krishna Pantakani
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Article |
Differentiation-dependent requirement of Tsix long non-coding RNA in imprinted X-chromosome inactivation
Imprinted mouse X-chromosome inactivation is controlled by two long non-coding RNAs, Tsix and Xist. Here, Maclary et al. demonstrate that Tsix is dispensable during the initiation and maintenance of X-inactivation in vivo and in vitro, but required to prevent Xist expression as trophectodermal progenitors differentiate.
- Emily Maclary
- , Emily Buttigieg
- & Sundeep Kalantry
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Involvement of parental imprinting in the antisense regulation of onco-miR-372-373
The miR-372-3 cluster has a role in oncogenesis. In this study, by utilizing parthenogenetic induced pluripotent stem cells, that lack the paternal genome, Stelzer et al.report that these miR-372-3 are negatively regulated by a paternally imprinted antisense transcript and that loss of its expression promotes oncogenesis.
- Yonatan Stelzer
- , Ido Sagi
- & Nissim Benvenisty
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| Open AccessThyroid hormone determines the start of the sensitive period of imprinting and primes later learning
Filial imprinting allows precocial birds to form social attachment to other animals or objects soon after hatching. Yamaguchi and colleagues investigate the mechanisms responsible for this, and find that thyroid hormones circulating in the plasma regulate the sensitive period during which imprinting occurs.
- Shinji Yamaguchi
- , Naoya Aoki
- & Koichi J. Homma