The continuing quest to comprehend genomic imprinting

Miyoshi, Naoki; Barton, Sheila C.; Kaneda, Masahiro; Hájková, Petra; Surani, M. Azim

doi:10.1159/000090808

Cited by 31 publications

(20 citation statements)

References 103 publications

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“…The high degree of purity of equid trophoblast preparations compared with placental isolations from mice may have reduced false-positive assignments caused by contaminating maternal tissues and facilitated the detection of paternal-expression bias in this extraembryonic lineage. This paternal-expression bias of imprinted genes is consistent with the early experiments in mouse embryo manipulation (8,37). Furthermore, our data provide a list of candidate genes that could produce the pattern of eCG levels in maternal serum described long ago for pregnant equids carrying intra-and interspecies pregnancies (17).…”

supporting

confidence: 87%

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Paternally expressed genes predominate in the placenta

Wang

Miller

Harman

et al. 2013

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

154

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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supporting

confidence: 87%

“…Paternally Expressed Imprinted Genes Predominate in Placenta. The discovery of imprinting through the construction of androgenetic and gynogenetic mice strongly suggested that the paternal genome has a major influence on placental development (8,37). Similar conclusions can be drawn from tissue development in human molar pregnancies (38,39).…”

mentioning

confidence: 62%

Paternally expressed genes predominate in the placenta

Wang

Miller

Harman

et al. 2013

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

154

143

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“…3,4 Imprinted genes encode either proteins or noncoding RNA (ncRNA), the majority of which have been shown to play critical roles in controlling embryonic growth and development. 5,6 Some imprinted genes are also known to encode DNA-binding proteins, such as Zac1 and Peg3. 7,8 The DNA-binding protein encoded by Zac1 binds to the 3 0 enhancer of H19 as a transcriptional activator, suggesting a functional connection between the 2 imprinted genes, paternally expressed Zac1 and maternally expressed H19.…”

Section: Introductionmentioning

confidence: 99%

PEG3 binds to H19-ICR as a transcriptional repressor

Kim

2016

Epigenetics

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Paternally expressed gene 3 (Peg3) encodes a DNA-binding protein with 12 C2H2 zinc finger motifs. In the current study, we performed ChIP-seq using mouse embryonic fibroblast (MEF) cells. This experiment identified a set of 16 PEG3 genomic targets, the majority of which overlapped with the promoter regions of genes with oocyte expression. These potential downstream genes were upregulated in MEF cells lacking PEG3 protein, suggesting a potential repressor role for PEG3. Our study also identified the imprinting control region (ICR) of H19 as a genomic target. According to the results, PEG3 binds to a specific sequence motif located between the 3 rd and 4 th CTCF binding sites of the H19-ICR. PEG3 also binds to the active maternal allele of the H19-ICR. The expression levels of H19 were upregulated in MEF cells lacking PEG3, and this upregulation was mainly derived from the maternal allele. This suggests that PEG3 may function as a transcriptional repressor for the maternal allele of H19. Overall, the current study uncovers a potential functional relationship between Peg3 and H19, and also confirms PEG3 as a transcriptional repressor for the identified downstream genes.

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“…Proper allelic expression of imprinted genes plays an important role in embryonic and neonatal growth, placental function, and postnatal behavior (2). Allele-specific DNA methylation at discrete regions established during gametogenesis defines the functional asymmetry of parental alleles (1).…”

mentioning

confidence: 99%

Characterization of global loss of imprinting in fetal overgrowth syndrome induced by assisted reproduction

Chen

Hagen

Elsik

et al. 2015

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

129

236

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Embryos generated with the use of assisted reproductive technologies (ART) can develop overgrowth syndromes. In ruminants, the condition is referred to as large offspring syndrome (LOS) and exhibits variable phenotypic abnormalities including overgrowth, enlarged tongue, and abdominal wall defects. These characteristics recapitulate those observed in the human loss-of-imprinting (LOI) overgrowth syndrome Beckwith-Wiedemann (BWS). We have recently shown LOI at the KCNQ1 locus in LOS, the most common epimutation in BWS. Although the first case of ARTinduced LOS was reported in 1995, studies have not yet determined the extent of LOI in this condition. Here, we determined allele-specific expression of imprinted genes previously identified in human and/or mouse in day ∼105 Bos taurus indicus × Bos taurus taurus F1 hybrid control and LOS fetuses using RNAseq. Our analysis allowed us to determine the monoallelic expression of 20 genes in tissues of control fetuses. LOS fetuses displayed variable LOI compared with controls. Biallelic expression of imprinted genes in LOS was associated with tissue-specific hypomethylation of the normally methylated parental allele. In addition, a positive correlation was observed between body weight and the number of biallelically expressed imprinted genes in LOS fetuses. Furthermore, not only was there loss of allele-specific expression of imprinted genes in LOS, but also differential transcript amounts of these genes between control and overgrown fetuses. In summary, we characterized previously unidentified imprinted genes in bovines and identified misregulation of imprinting at multiple loci in LOS. We concluded that LOS is a multilocus LOI syndrome, as is BWS.genomic imprinting | assisted reproductive technologies | large offspring syndrome | Beckwith-Wiedemann syndrome | loss of imprinting

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The continuing quest to comprehend genomic imprinting

Cited by 31 publications

References 103 publications

Paternally expressed genes predominate in the placenta

Paternally expressed genes predominate in the placenta

PEG3 binds to H19-ICR as a transcriptional repressor

Characterization of global loss of imprinting in fetal overgrowth syndrome induced by assisted reproduction

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