New insights on the role of DNA methylation from a global view

Meier, Karin; Recillas‐Targa, Félix

doi:10.2741/4508

Cited by 19 publications

(9 citation statements)

References 175 publications

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“…Fig. S2 ) which was as expected for actively transcribed genes (Meier and Recillas-Targa 2017 ). The comparison of mean CpG methylation level between groups revealed no significant effects on allelic imbalance of ACACA and SCD .…”

Section: Resultssupporting

confidence: 85%

Analysis of allele-specific expression of seven candidate genes involved in lipid metabolism in pig skeletal muscle and fat tissues reveals allelic imbalance of ACACA, LEP, SCD, and TNF

Stachowiak

Flisikowski

2019

J Appl Genetics

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Analysis of allele-specific expression may help to elucidate the genetic architecture of complex traits including fat deposition in pigs. Here, we used pyrosequencing to investigate the allele proportions of candidate genes ( ACACA , ADIPOR1 , FASN , LEP , ME1 , SCD , and TNF ) involved in regulation of lipid metabolism in two fat deposits (subcutaneous and visceral fat) and longissimus dorsi muscle of pigs representing Polish Large White, Polish Landrace, Duroc, and Pietrain breeds. We detected differential allelic expression of ACACA , LEP , SCD , and TNF in all tissues analyzed. To search for putative cis -regulatory elements involved in allele-specific expression, we quantified the methylation level within CpG islands located in 5′-flanking regions of ACACA and SCD . Comparison between samples showing markedly disproportionate allelic expression and control groups with similar levels of both alleles did not reveal significant differences. We also assessed the association of rs321308225 (c.*195C>A) an SNP located in the 3′UTR of ACACA with its allelic expression in Polish Landrace pigs, but it was not significant. We conclude that allelic imbalance occurs frequently in regard to genes involved in regulation of lipid deposition in pigs, and further studies are necessary to identify cis -regulatory elements affecting ACACA , LEP , SCD , and TNF expression in porcine fat tissues and skeletal muscle. Electronic supplementary material The online version of this article (10.1007/s13353-019-00485-z) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 85%

Analysis of allele-specific expression of seven candidate genes involved in lipid metabolism in pig skeletal muscle and fat tissues reveals allelic imbalance of ACACA, LEP, SCD, and TNF

Stachowiak

Flisikowski

2019

J Appl Genetics

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“…DNA methylation on cytosines occurs preferentially at CpG islands which are composed of a high GC base density and located at promoter or distal cis-regulatory elements, like enhancers. DNA methylation is catalyzed by DNA methyltransferases (DNMT) and is associated with gene silencing (44). At the post transcriptional level, noncoding RNA (ncRNA) can target complementary mRNA epigenetic and impair mRNA translation.…”

Section: Epigenetic Modifications In T Cellsmentioning

confidence: 99%

Epigenetic Reprogramming of CD4+ Helper T Cells as a Strategy to Improve Anticancer Immunotherapy

et al. 2021

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Evidences highlight the role of various CD4+ helper T cells (CD4+ Th) subpopulations in orchestrating the immune responses against cancers. Epigenetics takes an important part in the regulation of CD4+ Th polarization and plasticity. In this review, we described the epigenetic factors that govern CD4+ T cells differentiation and recruitment in the tumor microenvironment and their subsequent involvement in the antitumor immunity. Finally, we discussed how to manipulate tumor reactive CD4+ Th responses by epigenetic drugs to improve anticancer immunotherapy.

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“…CpG island methylation changes are involved in the regulation of gene expression and affect the structure of chromosomes. CpG islands are generally located in the promoter region of genes and contain binding sites for many transcription factors, and the methylation of this region prevents certain transcription factors from binding to them 15-20. Studies have found that the DNA methylation changes in several genes, such as RASSF1A 21-23, VHL 24-26, and EZH2 27, are associated with RCC and that DNA methylation changes could regulate the expression of these genes, ultimately leading to the development of RCC.…”

Section: Introductionmentioning

confidence: 99%

DNA methylation-regulated QPCT promotes sunitinib resistance by increasing HRAS stability in renal cell carcinoma

et al. 2019

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Rationale: Although sunitinib has been shown to improve the survival rate of advanced renal cell carcinoma (RCC) patients, poor drug response is a major challenge that reduces patient benefit. It is important to elucidate the underlying mechanism so that the therapeutic response to sunitinib can be restored.Methods: We used an Illumina HumanMethylation 850K microarray to find methylation-differentiated CpG sites between sunitinib-nonresponsive and -responsive RCC tissues and Sequenom MassARRAY methylation analysis to verify the methylation chip results. We verified glutaminyl peptide cyclotransferase (QPCT) expression in sunitinib-nonresponsive and -responsive RCC tissues via qRT-PCR, western blot and immunohistochemical assays. Then, cell counting kit 8 (CCK-8), plate colony formation and flow cytometric assays were used to verify the function of QPCT in RCC sunitinib resistance after QPCT intervention or overexpression. Chromatin immunoprecipitation (ChIP) was performed to clarify the upstream regulatory mechanism of QPCT. A human proteome microarray assay was used to identify downstream proteins that interact with QPCT, and co-immunoprecipitation (co-IP) and confocal laser microscopy were used to verify the protein chip results.Results: We found that the degree of methylation in the QPCT promoter region was significantly different between sunitinib-nonresponsive and -responsive RCC tissues. In the sunitinib-nonresponsive tissues, the degree of methylation in the QPCT promoter region was significantly reduced, and the expression of QPCT was upregulated, which correlated with a clinically poor response to sunitinib. A knockdown of QPCT conferred sunitinib sensitivity traits to RCC cells, whereas an overexpression of QPCT restored sunitinib resistance in RCC cells. Mechanistically, reducing the methylation degree of the QPCT promoter region by 5-aza-2'-deoxycytidine (decitabine) in RCC cells could increase the expression of QPCT and NF-κB (p65) bound to the QPCT promoter region, positively regulating its expression, while the hypermethylation in the QPCT promoter region could inhibit the binding of NF-κB (p65). QPCT could bind to HRAS and attenuate the ubiquitination of HRAS, thus increasing its stability and leading to the activation of the ERK pathway in RCC cells.Conclusion: QPCT may be a novel predictor of the response to sunitinib therapy in RCC patients and a potential therapeutic target.

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New insights on the role of DNA methylation from a global view

Cited by 19 publications

References 175 publications

Analysis of allele-specific expression of seven candidate genes involved in lipid metabolism in pig skeletal muscle and fat tissues reveals allelic imbalance of ACACA, LEP, SCD, and TNF

Analysis of allele-specific expression of seven candidate genes involved in lipid metabolism in pig skeletal muscle and fat tissues reveals allelic imbalance of ACACA, LEP, SCD, and TNF

Epigenetic Reprogramming of CD4+ Helper T Cells as a Strategy to Improve Anticancer Immunotherapy

DNA methylation-regulated QPCT promotes sunitinib resistance by increasing HRAS stability in renal cell carcinoma

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