Regulation of CpG methylation by Dnmt and Tet in pluripotent stem cells

Horii, Takuro; Hatada, Izuho

doi:10.1262/jrd.2016-046

Cited by 23 publications

(16 citation statements)

References 76 publications

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“…Our findings showed that less DNMT1 bound to the Ki-67 promoter in MKN45 cells than in HK-2 cells. As DNMT1 is a significant mediator in the process of DNA methylation, the Ki-67 promoter was hypomethylated in MKN45 cells, which was consistent with previous reports 39,40. Meanwhile, Sp1 and p300 tended to bind to Ki-67 promoter in MKN45 cells.…”

Section: Discussionsupporting

confidence: 91%

<p>Reciprocal Role Of DNA Methylation And Sp1 Binding In Ki-67 Gene Transcription</p>

Li¹,

Wang²,

Zhu³

et al. 2019

CMAR

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PurposeDNA methylation plays major regulatory roles in gene transcription. Our previous studies confirmed that Ki-67 promoter is hypomethylated and Sp1 is a transcriptional activator of Ki-67 gene in cancer cells. However, whether Sp1-mediated transcriptional activation of Ki-67 is related to its methylation has not been studied yet.Materials and methodsIn this study, we confirmed that methylated CpG binding protein 2 (MBD2) binding to methylated DNA hindered the binding of Sp1 to Ki-67 promoter and then repressed Ki-67 transcription through chromatin immunoprecipitation (ChIP) and quantitative real-time PCR (qRT-PCR). Co-immunoprecipitation (Co-IP), ChIP, methylation-specific PCR (MS-PCR) and Western blot were utilized to analyze the effects of Sp1 binding to Ki-67 promoter on its methylation status.ResultsLess DNA methyltransferase 1 (DNMT1) bound to the Ki-67 promoter in MKN45 cells than in HK-2 cells. Histone acetyltransferase p300 that was recruited by Sp1 to Ki-67 promoter could attenuate the methylation level of Ki-67 promoter. Furthermore, higher expression of Sp1 and Ki-67 was related to the overall survival (OS), first progression (FP) and post-progression survival (PPS) in gastric cancer by scrutinizing bioinformatics datasets.ConclusionTaken together, our findings suggested that hypomethylation of Ki-67 promoter enhanced the binding of Sp1, which in turn maintained hypomethylation of promoter, leading to increase Ki-67 expression in cancer cells. Sp1 and Ki-67 could act promising prognostic biomarkers for clinical diagnosis and treatment of cancer.

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Section: Discussionsupporting

confidence: 91%

<p>Reciprocal Role Of DNA Methylation And Sp1 Binding In Ki-67 Gene Transcription</p>

Li¹,

Wang²,

Zhu³

et al. 2019

CMAR

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“…We evaluated mRNA expressions for epigenetic modifiers such as Ten-eleven translocation (TET) enzymes and DNA methyltranferases (DNMTs) 11 , 26 . Postnatal ontogenic gene expression of TET enzymes showed that Tet1 mRNA levels were decreased in a time-dependent manner after birth, whereas both Tet2 and Tet3 mRNA levels were increased with a peak at D16 and declined thereafter.…”

Section: Resultsmentioning

confidence: 99%

Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood

et al. 2018

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The nutritional environment to which animals are exposed in early life can lead to epigenetic changes in the genome that influence the risk of obesity in later life. Here, we demonstrate that the fibroblast growth factor-21 gene (Fgf21) is subject to peroxisome proliferator-activated receptor (PPAR) α–dependent DNA demethylation in the liver during the postnatal period. Reductions in Fgf21 methylation can be enhanced via pharmacologic activation of PPARα during the suckling period. We also reveal that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood. Reduced DNA methylation is associated with enhanced induction of hepatic FGF21 expression after PPARα activation, which may partly explain the attenuation of diet-induced obesity in adulthood. We propose that Fgf21 methylation represents a form of epigenetic memory that persists into adulthood, and it may have a role in the developmental programming of obesity.

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“…TET1 and TET2 are important in demethylation process in cancerous and somatic cell development [Rasmussen and Helin, ]. Therefore, TET proteins can be considered a regulator of genome methylation patterns and can contribute to etiology of complex diseases [Hattori et al, ; Horii and Hatada, ].…”

mentioning

confidence: 99%

Novel Epigenetic Controlling of Hypoxia Pathway Related to Overexpression and Promoter Hypomethylation of TET1 and TET2 in RPE Cells

Alivand

Soheili

Pornour

et al. 2017

J of Cellular Biochemistry

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CpG methylation of DNA takes part in a specific epigenetic memory that plays crucial roles in the differentiation and abnormality of the cells. The methylation pattern aberration of genomes is affected in three ways, namely DNA methyltransferase (DNMT), ten-eleven translocation (TET), and methyl-binding domain (MBD) proteins. Of these, TET enzymes have recently been demonstrated to be master modifier enzymes in the DNA methylation process. Additionally, recent studies emphasize that not only epigenetic phenomena play a role in controlling hypoxia pathway, but the hypoxia condition also triggers hypomethylation of genomes that may help with the expression of hypoxia pathway genes. In this study, we suggested that TET1 and TET2 could play a role in the demethylation of genomes under chemical hypoxia conditions. Herein, the evaluating methylation status and mRNA expression of mentioned genes were utilized through real-time PCR and methylation-specific PCR (MSP), respectively. Our results showed that TET1 and TET2 genes were overexpressed (P < 0.05) under chemical hypoxia conditions in Retinal Pigment Epithelial (RPE) cells, whereas the promoter methylation status of them were hypomethylated in the same condition. Therefore, chemical hypoxia not only causes overexpression of TET1 and TET2 but also could gradually do promoter demethylation of same genes. This is the first study to show the relationship between epigenetics and the expression of mentioned genes related to hypoxia pathways. Furthermore, it seems that these associations in RPE cells are subjected to chemical hypoxia as a mechanism that could play a crucial role in methylation pattern changes of hypoxia-related diseases such as cancer and ischemia. J. Cell. Biochem. 118: 3193-3204, 2017. © 2017 Wiley Periodicals, Inc.

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Regulation of CpG methylation by Dnmt and Tet in pluripotent stem cells

Cited by 23 publications

References 76 publications

<p>Reciprocal Role Of DNA Methylation And Sp1 Binding In Ki-67 Gene Transcription</p>

<p>Reciprocal Role Of DNA Methylation And Sp1 Binding In Ki-67 Gene Transcription</p>

Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood

Novel Epigenetic Controlling of Hypoxia Pathway Related to Overexpression and Promoter Hypomethylation of TET1 and TET2 in RPE Cells

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