DNA Demethylation by DNMT3A and DNMT3B in vitro and of Methylated Episomal DNA in Transiently Transfected Cells

Chatterjee, Biswanath; Lin, Miao; Chen, Sean Chun-Chang; Peng, Kai; Wu, M.S.; Tseng, Mei‐Chun; Chen, Yu‐Ju; Shen, Che Kun James

doi:10.1016/j.bbagrm.2018.09.009

Cited by 8 publications

(7 citation statements)

References 38 publications

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“…The study displayed that high 5hmC content is an independent prognosis factor of unfavorable PFS and OS in pediatric SHCC. Low 5hmC contents in most solid tumors usually means higher tumor grade and worse results [3,11,13,14,27,28]. Nevertheless, our findings displayed that high 5hmC contents were independently relevant to inferior OS in SHCC and 5hmC was possibly correlated with tumor occurrence and malignant transformation.…”

Section: Disscusionmentioning

confidence: 54%

Global DNA 5hmC and CK19 with 5hmC positives cell contents represent a promising biomarker for predicting prognosis in small hepatocellular carcinoma

Jiang

Yan

Cui

et al. 2020

Preprint

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Background: 5-Hydroxymethylcytosine (5hmC) exists dynamically and exhibits various regulatory functions. It’s possibly associated with tumor occurrence and malignant transformation. Nevertheless, the part of 5hmC in small hepatocellular carcinoma (SHCC) is still elusive. The study was directed toward characterizing 5hmC content in SHCC and assessing if global genomic 5hmC content was able to serve as a promising factor for predicting clinical results.Methods: The expression contens of 5mC, 5hmC and 5fC were assesed using ultra-high performance liquid chromatography tandem mass-spectrometry(UHPLC-MS/MS). 5hmC contens and CK19 expression were measured by immunohistochemistry(IHC) .Results: The findings in the study displayed that global genomic 5mC, 5hmC, and 5fC contents in SHCC specimens were globally reduced relative to para-tumor tissues (P<0.001), Lymph node metastasis may be found in the small HCC, the non-metastasis group exhibited higher 5mC and 5hmc contents relative to those in metastasis group (P<0.001). HBV DNA was relevant to the decrease in 5mC, 5hmC and 5fC, as evidenced by the measurements in cell lines carrying or not carrying HBV DNA. Moreover, the correlation analysis showed the negative correlation of the content of 5hmC with CK19 expression in SHCC. The decreases of both 5hmC and CK19 with 5hmC positives cell contents in genomic DNA were related to SHCC patients’ unfavorable prognosis. Compared with para-tumor tissues, the 5hmC content in SHCC specimems was dramatically reduced.Conclusions: 5hmC and CK19 with 5hmC positives cell contents in genomic DNA possibly serve as a promising biomarker for predicting prognosis in small hepatocellular carcinoma.

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Section: Disscusionmentioning

confidence: 54%

Global DNA 5hmC and CK19 with 5hmC positives cell contents represent a promising biomarker for predicting prognosis in small hepatocellular carcinoma

Jiang

Yan

Cui

et al. 2020

Preprint

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“…This research demonstrates high 5hmC content acts as the prognostic factor to independently predict OS and PFS of SHCC. On the contrary, low 5hmC content of many solid tumors often suggests greater tumor grade as well as poor outcomes [3,11,13,19,25,32]. Whereas, the research showed the correlation of high 5hmC contents with good OS of SHCC, and 5hmC is linked to tumor occurrence or malignant transformation.…”

Section: Discussionmentioning

confidence: 92%

Global DNA 5hmC and CK195hmC+ Contents: A Promising Biomarker for Predicting Prognosis in Small Hepatocellular Carcinoma

2021

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Background: 5-Hydroxymethylcytosine (5hmC) with dynamic existence possesses multiple regulatory functions. Whereas, 5hmC’s impact on small hepatocellular carcinoma (SHCC) remains unclear. The present work focused on characterizing 5hmC content within SHCC and assessing the possibility of using global genomic 5hmC level as the predicative factor of clinical outcome. Methods: This study applied ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in measuring 5mC, 5fC and 5hmC contents. In addition, immunohistochemistry (IHC) was adopted to measure CK19 and 5hmC contents. Results: Research showed 5mC, 5hmC, and 5fC contents from global genomics of SHCC reduced extensively compared with healthy samples (p < 0.001). Moreover, SHCC was associated with lymph node metastasis (LNM). Greater 5mC and 5hmC levels were observed in non-metastasis group compared with the metastasis group (p < 0.001). Correlation analysis between the HBV DNA level and 5mC, 5fC and 5hmC levels exhibited that HBV DNA was associated with 5mC, 5hmC, and 5fC content reduction, which was verified in the cytological experiments. Moreover, 5hmC content had a negative correlation with the expression level of CK19 in SHCC. The decrease in 5hmC and CK19 containing 5hmC positive cell (called CK195hmC+) should be ascribed to the bad prognosis among SHCC patients. Conclusions: The contents of 5hmC and CK195hmC+ of genomic DNA might be adopted for predicting SHCC survival as an important biomarker.

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“…Interestingly, we identified a comparable number of hypo and hyper methylated regions in the PFC DKO neurons compared to controls. Considering the demonstrated influence of DNMT enzymes on demethylation and interdependencies in recruitment of DNMT and TET enzymes (Chatterjee et al, 2018; Chen et al, 2013a; Gu et al, 2018; Kangaspeska et al, 2008; Métivier et al, 2008; van der Wijst et al, 2015; Zhang et al, 2017), hyper methylated sites in the PFC DKO neurons are not surprising. Plausibly, this indicates that the presence of DNMT enzymes is essential for demethylation at these hypermethylated sites.…”

Section: Discussionmentioning

confidence: 99%

DNA Methyltransferase 1 and 3a Expression in the Frontal Cortex Regulates Palatable Food Consumption

Manjegowda

Joy-Gaba

Wengert

et al. 2021

Preprint

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DNA methylation is an important regulatory mechanism in the control of neuronal function. Both during development and following exposure to salient stimuli, plasticity in the methylation of cytosine residues leads to a change in neuron excitability that subsequently sculpts animal behavior. However, although the response of DNA methyltransferase enzymes in adult neurons to stimuli such as drugs of abuse have been described, less is known about how these enzymes regulate methylation at specific loci to change the drive to ingest natural rewards. Specifically, we do not understand how changes in methylation within important brain areas known to regulate palatable food intake can affect ingestion, while a detailed investigation of the neurophysiological and genomic effects of perturbing methyltransferase function has not been pursued. By deleting DNA methyltransferase 1 and 3a in the mouse prefrontal cortex, we observed the requirement for these enzymes in the regulation of nutrient rich food consumption in the absence of any effect on the intake of low fat and low sugar chow. We also determined that the deletion profoundly affected neuron excitability within pyramidal cells resident in superficial layers II/III of the cortex but had little effect in deep layer V neurons. Finally, reduced representation bisulfite sequencing revealed both hypo and hypermethylation in response to methyltransferase deletion, an effect that was observed in binding sites for retinoic acid receptor beta (RARβ) located within regulatory regions of genes known to affect neuronal function. Together, our data suggest that alterations in the actions of RARβ could shift neuronal activity to reduce palatable food intake.

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DNA Demethylation by DNMT3A and DNMT3B in vitro and of Methylated Episomal DNA in Transiently Transfected Cells

Cited by 8 publications

References 38 publications

Global DNA 5hmC and CK19 with 5hmC positives cell contents represent a promising biomarker for predicting prognosis in small hepatocellular carcinoma

Global DNA 5hmC and CK19 with 5hmC positives cell contents represent a promising biomarker for predicting prognosis in small hepatocellular carcinoma

Global DNA 5hmC and CK195hmC+ Contents: A Promising Biomarker for Predicting Prognosis in Small Hepatocellular Carcinoma

DNA Methyltransferase 1 and 3a Expression in the Frontal Cortex Regulates Palatable Food Consumption

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