Intergenic and Intronic DNA Hypomethylated Regions as Putative Regulators of Imprinted Domains

Bakshi, Arundhati; Bretz, Corey L.; Cain, Terri L; Kim, Joomyeong

doi:10.2217/epi-2017-0125

Cited by 11 publications

(7 citation statements)

References 56 publications

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“…This finding is consistent with previous studies by our own as well as other groups of investigators showing that DNA methylation events often involve regions other than promoters [15,42,43]. How gene body methylation may affect gene expression remains unclear [44][45][46]. However, our Methylome and Transcriptome findings in human FDR pre-adipocytes suggest that hypomethylation occurring at the gene body level may enhance gene expression; indeed, some genes in which both DNA methylation and mRNA expression were found simultaneously altered in the FDR pre-adipocytes show reduced methylation and increased expression.…”

Section: Discussionsupporting

confidence: 93%

Altered PTPRD DNA Methylation Associates with Restricted Adipogenesis in Healthy First-Degree Relatives of Type 2 Diabetes Subjects

Parrillo¹,

Spinelli²,

Longo³

et al. 2020

Epigenomics

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Aim: First-degree relatives (FDR) of individuals with Type 2 diabetes (T2D) feature restricted adipogenesis, which render them more vulnerable to T2D. Epigenetics may contribute to these abnormalities. Methods: FDR pre-adipocyte Methylome and Transcriptome were investigated by MeDIP- and RNA-Seq, respectively. Results: Methylome analysis revealed 2841 differentially methylated regions (DMR) in FDR. Most DMR localized into gene-body and were hypomethylated. The strongest hypomethylation signal was identified in an intronic-DMR at the PTPRD gene. PTPRD hypomethylation in FDR was confirmed by bisulphite sequencing and was responsible for its upregulation. Interestingly, Ptprd-overexpression in 3T3-L1 pre-adipocytes inhibited adipogenesis. Notably, the validated PTPRD-associated DMR was significantly hypomethylated in peripheral blood leukocytes from the same FDR individuals. Finally, PTPRD methylation pattern was also replicated in obese individuals. Conclusion: Our findings indicated a previously unrecognized role of PTPRD in restraining adipogenesis. This abnormality may contribute to increase FDR proclivity toward T2D.

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Section: Discussionsupporting

confidence: 93%

Altered PTPRD DNA Methylation Associates with Restricted Adipogenesis in Healthy First-Degree Relatives of Type 2 Diabetes Subjects

Parrillo¹,

Spinelli²,

Longo³

et al. 2020

Epigenomics

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“…These ECRs are usually marked with two histone modifications, H3K4me1 (mono-methylation on lysine 4 of histone 3) and H3K27ac (acetylation on lysine 27 of histone 3), suggesting potential enhancer roles for the transcription of Peg3 domain. One ECR, ECR18, has been shown to physically interact with the promoter of Peg3 / Usp29 , and also recently demonstrated to be a shared enhancer between the paternally expressed Peg3 / Usp29 and the maternally expressed Zim1 [17]. However, the functional contribution of the majority of these ECRs to the imprinting of the Peg3 domain has not been examined.…”

Section: Introductionmentioning

confidence: 99%

Allele-specific enhancer interaction at the Peg3 imprinted domain

et al. 2019

Self Cite

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The parental allele specificity of mammalian imprinted genes has been evolutionarily well conserved, although its functional constraints and associated mechanisms are not fully understood. In the current study, we generated a mouse mutant with switched active alleles driving the switch from paternal-to-maternal expression for Peg3 and the maternal-to-paternal expression for Zim1. The expression levels of Peg3 and Zim1, but not the spatial expression patterns, within the brain showed clear differences between wild type and mutant animals. We identified putative enhancers localized upstream of Peg3 that displayed allele-biased DNA methylation, and that also participate in allele-biased chromosomal conformations with regional promoters. Most importantly, these data suggest for the first time that long-distance enhancers may contribute to allelic expression within imprinted domains through allele-biased interactions with regional promoters.

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“…The CG methylation level was higher in WYG7 lines inactive gene and 5’UTR regions than in Ox1 in N deficiency condition. There are also reports showing the enrichment of DMRs in the intron and intergenic regions, and promoters with conserved and functional regulation of transcription [ 50 , 51 ]. We found the total methylation level was higher in Ox1 lines in promoter and intergenic regions (Fig.…”

Section: Discussionmentioning

confidence: 99%

Plant DNA methylation is sensitive to parent seed N content and influences the growth of rice

Fan

Liu²,

Qian

et al. 2021

BMC Plant Biol

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Background Nitrogen (N) is an important nutrient for plant growth, development, and agricultural production. Nitrogen stress could induce epigenetic changes in plants. In our research, overexpression of the OsNAR2.1 line was used as a testing target in rice plants with high nitrogen-use efficiency to study the changes of rice methylation and growth in respond of the endogenous and external nitrogen stress. Results Our results showed that external N deficiency could decrease seed N content and plant growth of the overexpression line. During the filial growth, we found that the low parent seed nitrogen (LPSN) in the overexpression line could lead to a decrease in the filial seed nitrogen content, total plant nitrogen content, yield, and OsNAR2.1 expression (28, 35, 23, and 55%, respectively) compared with high parent seed nitrogen (HPSN) in high nitrogen external supply. However, such decreases were not observed in wild type. Furthermore, methylation sequencing results showed that LPSN caused massive gene methylation changes, which enriched in over 20 GO pathways in the filial overexpression line, and the expression of OsNAR2.1 in LPSN filial overexpression plants was significantly reduced compared to HPSN filial plants in high external N, which was not shown in wild type. Conclusions We suggest that the parent seed nitrogen content decreased induced DNA methylation changes at the epigenetic level and significantly decreased the expression of OsNAR2.1, resulting in a heritable phenotype of N deficiency over two generations of the overexpression line.

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Intergenic and Intronic DNA Hypomethylated Regions as Putative Regulators of Imprinted Domains

Cited by 11 publications

References 56 publications

Altered PTPRD DNA Methylation Associates with Restricted Adipogenesis in Healthy First-Degree Relatives of Type 2 Diabetes Subjects

Altered PTPRD DNA Methylation Associates with Restricted Adipogenesis in Healthy First-Degree Relatives of Type 2 Diabetes Subjects

Allele-specific enhancer interaction at the Peg3 imprinted domain

Plant DNA methylation is sensitive to parent seed N content and influences the growth of rice

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