DNA Demethylation Reactivates a Subset of Imprinted Genes in Uniparental Mouse Embryonic Fibroblasts

Kharroubi, Aboubaker El; Piras, Graziella; Stewart, Colin L.

doi:10.1074/jbc.m009392200

Cited by 78 publications

(74 citation statements)

References 48 publications

(49 reference statements)

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“…Treatment of cultured mule cells with a demethylating reagent or an inhibitor of histone deacetylase resulted in biallelic expression of H19 and IGF2, respectively, as has been shown in mice ( Fig. 2 and SI Appendix, SI Methods) (27), providing further evidence that imprinting in horse × donkey hybrid tissue is not disrupted.…”

Section: Genomic Imprinting and Epigenetic Reprogramming Are Properlysupporting

confidence: 71%

Paternally expressed genes predominate in the placenta

Wang

Miller

Harman

et al. 2013

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

147

143

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The discovery of genomic imprinting through studies of manipulated mouse embryos indicated that the paternal genome has a major influence on placental development. However, previous research has not demonstrated paternal bias in imprinted genes. We applied RNA sequencing to trophoblast tissue from reciprocal hybrids of horse and donkey, where genotypic differences allowed parent-of-origin identification of most expressed genes. Using this approach, we identified a core group of 15 ancient imprinted genes, of which 10 were paternally expressed. An additional 78 candidate imprinted genes identified by RNA sequencing also showed paternal bias. Pyrosequencing was used to confirm the imprinting status of six of the genes, including the insulin receptor ( INSR ), which may play a role in growth regulation with its reciprocally imprinted ligand, histone acetyltransferase-1 ( HAT1 ), a gene involved in chromatin modification, and lymphocyte antigen 6 complex, locus G6C, a newly identified imprinted gene in the major histocompatibility complex. The 78 candidate imprinted genes displayed parent-of-origin expression bias in placenta but not fetus, and most showed less than 100% silencing of the imprinted allele. Some displayed variability in imprinting status among individuals. This variability results in a unique epigenetic signature for each placenta that contributes to variation in the intrauterine environment and thus presents the opportunity for natural selection to operate on parent-of-origin differential regulation. Taken together, these features highlight the plasticity of imprinting in mammals and the central importance of the placenta as a target tissue for genomic imprinting.

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Section: Genomic Imprinting and Epigenetic Reprogramming Are Properlysupporting

confidence: 71%

Paternally expressed genes predominate in the placenta

Wang

Miller

Harman

et al. 2013

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

147

143

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“…This report also showed imprinting of Lot1/Zac1 on mouse chromosome 10 (the rat ortologue of Lot1 is located on chromosome 1p13) (Szpirer et al, 2001). Also, a subtractive screen using a cDNA library prepared from novel parthenogenetic and wild-type fibroblast lines identified Lot1 as an imprinted gene in mice (Piras et al, 2000;El Kharroubi et al, 2001). Zac1/Lot1 was expressed predominantly from the paternal allele in all adult mouse tissues (pituitary, ovary, lung, brain, and heart tissue) (Piras et al, 2000).…”

Section: Imprinting and Chromosomal Duplicationmentioning

confidence: 99%

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

Abdollahi

2006

Journal Cellular Physiology

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Lost-on-transformation 1 (LOT1) (PLAGL1/ZAC1) is a member of the novel subfamily of zinc-finger transcription factors, designated as PLAG family. The other members in this group include PLAG1 and PLAGL2, which share high homology with each other and with LOT1, particularly in their zinc-finger amino-terminal region. They are structurally similar but functionally different. For example, the LOT1 gene encodes a growth suppressor protein and is localized on human chromosome 6q24-25, a chromosomal region that is frequently deleted in many types of human cancers. The gene is maternally imprinted and is linked to developmental disorders such as growth retardation and transient neonatal diabetes mellitus (TNDM). LOT1 is a target of growth factor signaling pathway(s) and silenced by epigenetic mechanisms, as well as by the loss of heterozygosity in different tumor tissues. PLAG1 is a protooncogene that is localized on chromosome 8q12 and was found to be a target of several types of chromosomal rearrangement including the one identified in pleomorphic adenomas of the salivary gland. Since the discovery of the PLAG family members in 1997, much has been learned about their structure and function, as are summarized in this review. While the available data suggest that these proteins may play important roles in regulating normal physiological functions in the mammals, a great deal more about their signaling pathway(s), potential role in the complex pathologies such as cancer and developmental disorders, and functional relationship between different family members and splice variants still remains to be uncovered.

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“…The maternal allele of Sgce is silenced; paternal allele active (Piras et al, 2000;El Kharroubi et al, 2001). This gene encodes sarcoglycan-epsilon; one of five members of the sarcoglycan family, which are components of the dystrophin-sarcoglycan complex in muscle and in other tissues (Bonnemann et al, 1996;Ettinger et al, 1997).…”

Section: Imprinted Genes Expressedmentioning

confidence: 99%

Physiological functions of imprinted genes

Tycko

Morison

2002

Journal Cellular Physiology

290

203

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Genomic imprinting in gametogenesis marks a subset of mammalian genes for parent-of-origin-dependent monoallelic expression in the offspring. Embryological and classical genetic experiments in mice that uncovered the existence of genomic imprinting nearly two decades ago produced abnormalities of growth or behavior, without severe developmental malformations. Since then, the identification and manipulation of individual imprinted genes has continued to suggest that the diverse products of these genes are largely devoted to controlling pre-and post-natal growth, as well as brain function and behavior. Here, we review this evidence, and link our discussion to a website (http://www.otago.ac.nz/IGC) containing a comprehensive database of imprinted genes. Ultimately, these data will answer the long-debated question of whether there is a coherent biological rationale for imprinting.

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DNA Demethylation Reactivates a Subset of Imprinted Genes in Uniparental Mouse Embryonic Fibroblasts

Cited by 78 publications

References 48 publications

Paternally expressed genes predominate in the placenta

Paternally expressed genes predominate in the placenta

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

Physiological functions of imprinted genes

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