Establishment of DNA methylation patterns of the &lt;i&gt;Fibrillin1&lt;/i&gt; (&lt;i&gt;FBN1&lt;/i&gt;) gene in porcine embryos and tissues

Arai, Yoshikazu; Umeyama, Kazuhiro; Takeuchi, Kikuko; Okazaki, Natsumi; Hichiwa, Naomi; Yashima, Sayaka; Nakano, K.; Nagashima, Hiroshi; Ohgane, Jun

doi:10.1262/jrd.2016-158

Cited by 9 publications

(5 citation statements)

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“…DNA methylation has been reported to regulate the basic DNA sequence transcription potential in pigs and mice by changing the chromatin density and DNA accessibility to the cytoplasm [30][31][32]. The abnormal expression of DNMTs in donor cells results in DNA methylation defects and aberrant embryo development in pigs [33].…”

Section: Discussionmentioning

confidence: 99%

Dynamic Methylation Changes of DNA and H3K4 by RG108 Improve Epigenetic Reprogramming of Somatic Cell Nuclear Transfer Embryos in Pigs

Zhai

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: DNA methylation and histone modifications are essential epigenetic marks that can significantly affect the mammalian somatic cell nuclear transfer (SCNT) embryo development. However, the mechanisms by which the DNA methylation affects the epigenetic reprogramming have not been fully elucidated. Methods: In our study, we used quantitative polymerase chain reaction (qPCR), Western blotting, immunofluorescence staining (IF) and sodium bisulfite genomic sequencing to examine the effects of RG108, a DNA methyltransferase inhibitor (DNMTi), on the dynamic pattern of DNA methylation and histone modifications in porcine SCNT embryos and investigate the mechanism by which the epigenome status of donor cells’ affects SCNT embryos development and the crosstalk between epigenetic signals. Results: Our results showed that active DNA demethylation was enhanced by the significantly improving expression levels of TET1, TET2, TET3 and 5hmC, and passive DNA demethylation was promoted by the remarkably inhibitory expression levels of DNMT1, DNMT3A and 5mC in embryos constructed from the fetal fibroblasts (FFs) treated with RG108 (RG-SCNT embryos) compared to the levels in embryos from control FFs (FF-SCNT embryos). The signal intensity of histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 9 acetylation (H3K9Ac) was significantly increased and the expression levels of H3K4 methyltransferases were more than 2-fold higher expression in RG-SCNT embryos. RG-SCNT embryos had significantly higher cleavage and blastocyst rates (69.3±1.4%, and 24.72±2.3%, respectively) than FF-SCNT embryos (60.1±2.4% and 18.38±1.9%, respectively). Conclusion: Dynamic changes in DNA methylation caused by RG108 result in dynamic alterations in the patterns of H3K4me3, H3K9Ac and histone H3 lysine 9 trimethylation (H3K9me3), which leads to the activation of embryonic genome and epigenetic modification enzymes associated with H3K4 methylation, and contributes to reconstructing normal epigenetic modifications and improving the developmental efficiency of porcine SCNT embryos.

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Section: Discussionmentioning

confidence: 99%

Dynamic Methylation Changes of DNA and H3K4 by RG108 Improve Epigenetic Reprogramming of Somatic Cell Nuclear Transfer Embryos in Pigs

Zhai

Zhang

et al. 2018

Cell Physiol Biochem

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“…DNA methylation and histone modification (e.g., lysine acetylation and methylation, and/or arginine methylation) regulate chromatin density and DNA accessibility, and consequently gene transcription in pigs, mice, and humans (Arai et al, ; Cedar & Bergman, ; Reik, ; Straussman et al, ). These modifications are added and removed by specific enzymes, whose abundance can influence development.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic states of donor cells significantly affect the development of somatic cell nuclear transfer (SCNT) embryos in pigs

Zhai

Zhang

et al. 2017

Molecular Reproduction Devel

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The type and pattern of epigenetic modification in donor cells can significantly affect the developmental competency of somatic cell nuclear transfer (SCNT) embryos. Here, we investigated the developmental capacity, gene expression, and epigenetic modifications of SCNT embryos derived from porcine bone marrow-derived mesenchymal stem cells (BMSCs) and fetal fibroblasts (FFs) donor cells compared to embryos obtained from in vitro fertilization (IVF). Compared to FFs, the donor BMSCs had more active epigenetic markers (Histone H3 modifications: H3K9Ac, H3K4me3, and H3K4me2) and fewer repressive epigenetic markers (H3K9me3, H3K9me2, and DNA methyltransferase 1). Embryos derived from BMSC nuclear-transfer (BMSC-NT embryos) and IVF embryos had significantly higher cleavage and blastocyst rates (BMSC-NT: 71.3 ± 3.4%, 29.1 ± 2.3%; IVF: 69.2 ± 2.2%, 30.2 ± 3.3%; respectively) than FF-NT embryos (58.1 ± 3.4%, 15.1 ± 1.5%, respectively). Bisulfite sequencing revealed that DNA methylation at the promoter regions of NANOG and POU5F1 was lower in BMSC-NT embryos (30.0%, 9.8%, respectively) than those in FF-NT embryos (34.2%, 28.0%, respectively). We also found that BMSC-NT embryos had more H3K9Ac and less H3K9me3 and 5-methylcytosine than FF-NT embryos. In conclusion, our finding comparing BMSCs versus FFs as donors for nuclear transfer revealed that differences in the initial epigenetic state of donor cells have a remarkable effect on overall nuclear reprogramming of SCNT embryos, wherein donor cells possessing a more open chromatin state are more conducive to nuclear reprogramming.

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“…Based on findings from others [ 8 , 14 , 17 ], it was anticipated we would identify differently methylated loci surrounding the FBN1 gene that may influence FBN1 expression. However, we were not able to strengthen these results with our own findings.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, DNA-hypomethylation patterns of CpG-island shores of the FBN1-gene were associated with the level of FBN1 gene expression in porcine liver and fetal fibroblasts, showing its involvement in tissue/cell-type-specific gene expression [ 14 ]. To our knowledge, no other studies concerning the role of methylation patterns in MFS patients have been performed yet.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide methylation patterns in Marfan syndrome

et al. 2021

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Background Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the Fibrillin-1 gene (FBN1). Here, we undertook the first epigenome-wide association study (EWAS) in patients with MFS aiming at identifying DNA methylation loci associated with MFS phenotypes that may shed light on the disease process. Methods The Illumina 450 k DNA-methylation array was used on stored peripheral whole-blood samples of 190 patients with MFS originally included in the COMPARE trial. An unbiased genome-wide approach was used, and methylation of CpG-sites across the entire genome was evaluated. Additionally, we investigated CpG-sites across the FBN1-locus (15q21.1) more closely, since this is the gene defective in MFS. Differentially Methylated Positions (DMPs) and Differentially Methylated Regions (DMRs) were identified through regression analysis. Associations between methylation levels and aortic diameters and presence or absence of 21 clinical features of MFS at baseline were analyzed. Moreover, associations between aortic diameter change, and the occurrence of clinical events (death any cause, type-A or -B dissection/rupture, or aortic surgery) and methylation levels were analyzed. Results We identified 28 DMPs that are significantly associated with aortic diameters in patients with MFS. Seven of these DMPs (25%) could be allocated to a gene that was previously associated with cardiovascular diseases (HDAC4, IGF2BP3, CASZ1, SDK1, PCDHGA1, DIO3, PTPRN2). Moreover, we identified seven DMPs that were significantly associated with aortic diameter change and five DMP’s that associated with clinical events. No significant associations at p < 10–8 or p < 10–6 were found with any of the non-cardiovascular phenotypic MFS features. Investigating DMRs, clusters were seen mostly on X- and Y, and chromosome 18–22. The remaining DMRs indicated involvement of a large family of protocadherins on chromosome 5, which were not reported in MFS before. Conclusion This EWAS in patients with MFS has identified a number of methylation loci significantly associated with aortic diameters, aortic dilatation rate and aortic events. Our findings add to the slowly growing literature on the regulation of gene expression in MFS patients.

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Establishment of DNA methylation patterns of the <i>Fibrillin1</i> (<i>FBN1</i>) gene in porcine embryos and tissues

Cited by 9 publications

References 40 publications

Dynamic Methylation Changes of DNA and H3K4 by RG108 Improve Epigenetic Reprogramming of Somatic Cell Nuclear Transfer Embryos in Pigs

Dynamic Methylation Changes of DNA and H3K4 by RG108 Improve Epigenetic Reprogramming of Somatic Cell Nuclear Transfer Embryos in Pigs

Epigenetic states of donor cells significantly affect the development of somatic cell nuclear transfer (SCNT) embryos in pigs

Genome-wide methylation patterns in Marfan syndrome

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