Expression of KCNQ1OT1, CDKN1C, H19, and PLAGL1 and the methylation patterns at the KvDMR1 and H19/IGF2 imprinting control regions is conserved between human and bovine

Robbins, Katherine; Chen, Zhiyuan; Wells, Kevin D.; Rivera, Rocío Melissa

doi:10.1186/1423-0127-19-95

Cited by 44 publications

(55 citation statements)

References 71 publications

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“…The remaining 33 genes were not assessable in our system. RNAseq analysis confirmed the maternal expression of CDKN1C, H19, and PHLDA2 and the paternal expression of IGF2 and PLAGL1 (29,42). In addition, we demonstrated paternal expression of NNAT, NAP1L5, MAGEL2, PEG3, PEG10, SGCE, and SNRPN, which is similar to what has been reported for human and mouse (43).…”

Section: Discussionsupporting

confidence: 73%

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.

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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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Section: Discussionsupporting

confidence: 73%

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.

Self Cite

128

236

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“…The digested PCR products were resolved by polyacrylamide gel electrophoresis (PAGE). The assay used to determine allele-specific expression of H19 was previously described 31 . Allelic expression of PHLDA2 and IGF2 were determined by RT-PCR-SSCP (single strand conformation polymorphism) because restriction enzymes that recognized the sequence of interest were not available.…”

Section: Methodsmentioning

confidence: 99%

Large offspring syndrome

et al. 2013

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Beckwith-Wiedemann syndrome (BWS) is a human loss-of-imprinting syndrome primarily characterized by macrosomia, macroglossia, and abdominal wall defects. BWS has been associated with misregulation of two clusters of imprinted genes. Children conceived with the use of assisted reproductive technologies (ART) appear to have an increased incidence of BWS. As in humans, ART can also induce a similar overgrowth syndrome in ruminants which is referred to as large offspring syndrome (LOS). The main goal of our study is to determine if LOS shows similar loss-of-imprinting at loci known to be misregulated in BWS. To test this, Bos taurus indicus × Bos taurus taurus F1 hybrids were generated by artificial insemination (AI; control) or by ART. Seven of the 27 conceptuses in the ART group were in the > 97th percentile body weight when compared with controls. Further, other characteristics reported in BWS were observed in the ART group, such as large tongue, umbilical hernia, and ear malformations. KCNQ1OT1 (the most-often misregulated imprinted gene in BWS) was biallelically-expressed in various organs in two out of seven overgrown conceptuses from the ART group, but shows monoallelic expression in all tissues of the AI conceptuses. Furthermore, biallelic expression of KCNQ1OT1 is associated with loss of methylation at the KvDMR1 on the maternal allele and with downregulation of the maternally-expressed gene CDKN1C. In conclusion, our results show phenotypic and epigenetic similarities between LOS and BWS, and we propose the use of LOS as an animal model to investigate the etiology of BWS.

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“…maps at 11p15.5 (Table 3) and is located inside of a chromosomal R-band and could be considered as an example for a non-protein coding gene whose transcribed RNA is critical in the chromatin conformation 82-84. This was substantiated with recent data of gene expression comparison studies of differently structured genes and methylation patterns pivotal in gene regulation showing a high conservation between human and bovine 85.…”

Section: Discussionmentioning

confidence: 58%

Spatial Localization of Genes Determined by Intranuclear DNA Fragmentation with the Fusion Proteins Lamin KRED and Histone KRED und Visible Light

Waldeck¹,

Mueller²,

Glatting³

et al. 2013

Int. J. Med. Sci.

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The highly organized DNA architecture inside of the nuclei of cells is accepted in the scientific world. In the human genome about 3 billion nucleotides are organized as chromatin in the cell nucleus. In general, they are involved in gene regulation and transcription by histone modification. Small chromosomes are localized in a central nuclear position whereas the large chromosomes are peripherally positioned. In our experiments we inserted fusion proteins consisting of a component of the nuclear lamina (lamin B1) and also histone H2A, both combined with the light inducible fluorescence protein KillerRed (KRED). After activation, KRED generates reactive oxygen species (ROS) producing toxic effects and may cause cell death. We analyzed the spatial damage distribution in the chromatin after illumination of the cells with visible light. The extent of DNA damage was strongly dependent on its localization inside of nuclei.The ROS activity allowed to gain information about the location of genes and their functions via sequencing and data base analysis of the double strand breaks of the isolated DNA. A connection between the damaged gene sequences and some diseases was found.

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Expression of KCNQ1OT1, CDKN1C, H19, and PLAGL1 and the methylation patterns at the KvDMR1 and H19/IGF2 imprinting control regions is conserved between human and bovine

Cited by 44 publications

References 71 publications

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

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

Large offspring syndrome

Spatial Localization of Genes Determined by Intranuclear DNA Fragmentation with the Fusion Proteins Lamin KRED and Histone KRED und Visible Light

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