Altered methylation of IGF2 DMR0 is associated with neural tube defects

Wu, Lihua; Wang, Li; Shangguan, Shaofang; Chang, Shaoyan; Wang, Zhen; Lü, Xiaolin; Zhang, Qin; Wang, Jianhua; Zhao, Hengyu; Wang, Fang; Guo, Jin; Niu, Bo; Guo, Junyu; Zhang, Ting

doi:10.1007/s11010-013-1655-1

Cited by 25 publications

(21 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neural tube defect was reported in correlation with gene imprinting (Bai et al, 2014; Wang et al, 2017; Wu et al, 2013). Supplemental intake of formate during pregnancy was suggested as a method of preventing some neural tube defects owing to its function as methyl donor (Caffrey, McNulty, Irwin, Walsh, & Pentieva, 2018; Rochtus, Jansen, Van Geet, & Freson, 2015).…”

Section: Discussionmentioning

confidence: 99%

Deletion of BAF250a affects oocyte epigenetic modifications and embryonic development

Zhou

Meng

et al. 2020

Molecular Reproduction Devel

View full text Add to dashboard Cite

BRG1-associated factor 250a (BAF250a) is a component of the SWI/SNF adenosine triphosphate-dependent chromatin remodeling complex, which has been shown to control chromatin structure and transcription. BAF250a was reported to be a key component of the gene regulatory machinery in embryonic stem cells controlling self-renewal, differentiation, and cell lineage decisions. Here we constructed Baf250a F/F ;Gdf9-cre (Baf250a CKO ) mice to specifically delete BAF250a in oocytes to investigate the role of maternal BAF250a in female germ cells and embryo development. Our results showed that BAF250a deletion did not affect folliculogenesis, ovulation, and fertilization, but it caused late embryonic death. RNA sequencing analysis showed that the expression of genes involved in cell proliferation and differentiation, tissue morphogenesis, histone modification, and nucleosome remodeling were perturbed in Baf250a CKO MII oocytes. We showed that covalent histone modifications such as H3K27me3 and H3K27ac were also significantly affected in oocytes, which may reduce oocyte quality and lead to birth defects. In addition, the DNA methylation level of Igf2r, Snrpn, and Peg3 differentially methylated regions was decreased in Baf250a CKO oocytes. Quantitative real-time polymerase chain reaction analysis showed that the relative messenger RNA (mRNA) expression levels of Igf2r and Snrpn were significantly increased. The mRNA expression level of Dnmt1, Dnmt3a, Dnmt3l, and Uhrf1 was decreased, and the protein expression in these genes was also reduced, which might be the cause for impaired imprinting establishment. In conclusion, our results demonstrate that BAF250a plays an important role in oocyte transcription regulation, epigenetic modifications, and embryo development.BAF250a, epigenetic modification, oocyte maturation, SWI/SNF complex Abbreviations: Arid1a, AT-rich interactive domain 1 A gene; BAF250a, BRG1-associated factor 250a; DMR, differentially methylated region; DNMT, DNA methylation transferase; Ezh2, enhancer of zeste homolog 2; GV, germinal vesicle; H&E, hematoxylin and eosin; IOD, integrated optical density; MII, metaphase II; NSN, nonsurrounded nucleolus; NTD, neural tube defect; PMSG, pregnant mare serum gonadotropin; SN, surrounded nucleolus; TrxG, trithorax group protein; UHRF1, ubiquitin-like with PHD and ring finger domains 1; ZGA, zygotic genome activation. 552| ZHOU ET AL.

show abstract

Section: Discussionmentioning

confidence: 99%

Deletion of BAF250a affects oocyte epigenetic modifications and embryonic development

Zhou

Meng

et al. 2020

Molecular Reproduction Devel

View full text Add to dashboard Cite

show abstract

“…Besides vague effect of global DNA methylation, disruption of methylation at specific genes has been linked to NTDs, such as imprinted genes, 9,10 transposon genes, 7 DNA repair genes, 11 planar-cell polarity genes, 12 folate receptor genes, 13 and HOX genes. 14 Hypermethylation or hypomethylation of these specific genes was identified in NTD cases by targeted gene methylation profiling.…”

Section: Introductionmentioning

confidence: 99%

Fetal DNA hypermethylation in tight junction pathway is associated with neural tube defects: A genome-wide DNA methylation analysis

et al. 2017

View full text Add to dashboard Cite

Neural tube defects (NTDs) are a spectrum of severe congenital malformations of fusion failure of the neural tube during early embryogenesis. Evidence on aberrant DNA methylation in NTD development remains scarce, especially when exposure to environmental pollutant is taken into consideration. DNA methylation profiling was quantified using the Infinium HumanMethylation450 array in neural tissues from 10 NTD cases and 8 non-malformed controls (stage 1). Subsequent validation was performed using a Sequenom MassARRAY system in neural tissues from 20 NTD cases and 20 non-malformed controls (stage 2). Correlation analysis of differentially methylated CpG sites in fetal neural tissues and polycyclic aromatic hydrocarbons concentrations in fetal neural tissues and maternal serum was conducted. Differentially methylated CpG sites of neural tissues were further validated in fetal mice with NTDs induced by benzo(a)pyrene given to pregnant mice. Differentially hypermethylated CpG sites in neural tissues from 17 genes and 6 pathways were identified in stage 1. Subsequently, differentially hypermethylated CpG sites in neural tissues from 6 genes (BDKRB2, CTNNA1, CYFIP2, MMP7, MYH2, and TIAM2) were confirmed in stage 2. Correlation analysis showed that methylated CpG sites in CTNNA1 and MYH2 from NTD cases were positively correlated to polycyclic aromatic hydrocarbon level in fetal neural tissues and maternal serum. The correlation was confirmed in NTD-affected fetal mice that were exposed to benzo(a)pyrene in utero. In conclusion, hypermethylation of the CTNNA1 and MYH2 genes in tight junction pathway is associated with the risk for NTDs, and the DNA methylation aberration may be caused by exposure to benzo(a)pyrene.

show abstract

“…H19 DMR1 is conserved in mice, but Igf2 DMR0 is placenta-specific [3] . Several studies have indicated that IGF2 -relevant DMRs are potentially associated with NTDs [7] – [10] . In our present NTD cohort, Wu et al reported that hypermethylated IGF2 DMR0 is associated with the NTD-affected cohort [10] .…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have indicated that IGF2 -relevant DMRs are potentially associated with NTDs [7] – [10] . In our present NTD cohort, Wu et al reported that hypermethylated IGF2 DMR0 is associated with the NTD-affected cohort [10] . In contrast, Liu et al reported that the H19 DMR1 was hypermethylated, whereas the IGF2 DMR0 had no significant differences in the NTD and control cohorts [8] .…”

Section: Introductionmentioning

confidence: 99%

Different Epigenetic Alterations Are Associated with Abnormal IGF2/Igf2 Upregulation in Neural Tube Defects

et al. 2014

Self Cite

View full text Add to dashboard Cite

The methylation status of DNA methylation regions (DMRs) of the imprinted gene IGF2/Igf2 is associated with neural tube defects (NTDs), which are caused by a failure of the neural tube to fold and close and are the second-most common birth defect; however, the characterization of the expression level of IGF2/Igf2 in neural tissue from human fetuses affected with NTDs remains elusive. More importantly, whether abnormal chromatin structure also influences IGF2/Igf2 expression in NTDs is unclear. Here, we investigated the transcriptional activity of IGF2/Igf2 in normal and NTD spinal cord tissues, the methylation status of different DMRs, and the chromatin structure of the promoter. Our data indicated that in NTD samples from both human fetuses and retinoic acid (RA)-treated mouse fetuses, the expression level of IGF2/Igf2 was upregulated 6.41-fold and 1.84-fold, respectively, compared to controls. H19 DMR1, but not IGF2 DMR0, was hypermethylated in human NTD samples. In NTD mice, h19 DMR1 was stable, whereas the chromatin structure around the promoter of Igf2 might be loosened, which was displayed by higher H3K4 acetylation and lower H3K27 trimethylation. Therefore, the data revealed that IGF2/Igf2 expression can be ectopically up-regulated by dual epigenetic factors in NTDs. In detail, the upregulation of IGF2/Igf2 is likely controlled by hypermethylation of H19 DMR1 in human NTDs, however, in acute external RA-induced NTD mice it is potentially determined by more open chromatin structure.

show abstract

Altered methylation of IGF2 DMR0 is associated with neural tube defects

Cited by 25 publications

References 35 publications

Deletion of BAF250a affects oocyte epigenetic modifications and embryonic development

Deletion of BAF250a affects oocyte epigenetic modifications and embryonic development

Fetal DNA hypermethylation in tight junction pathway is associated with neural tube defects: A genome-wide DNA methylation analysis

Different Epigenetic Alterations Are Associated with Abnormal IGF2/Igf2 Upregulation in Neural Tube Defects

Contact Info

Product

Resources

About