GeneDMRs: An R Package for Gene-Based Differentially Methylated Regions Analysis

Wang, Xiao; Hao, Dan; Kadarmideen, Haja N.

doi:10.1089/cmb.2020.0081

Cited by 6 publications

(3 citation statements)

References 36 publications

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“…q Values < 0.05 and methylation difference ≥ 25%. B Scheme of CpGi, promoters, and gene body modified from Wang et al [ 2 ] (upper) and distribution of DMRs (lower). DMRs of CpG site are mainly intergenic regions.…”

Section: Resultsmentioning

confidence: 99%

Methionine regulates self-renewal, pluripotency, and cell death of GIC through cholesterol—rRNA axis

et al. 2022

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Background Glioma-initiating cells (GICs) are the source of glioma cells that can self-renew, have pluripotency, and are treatment-resistant, so are the starting point for relapse and eventual death despite multimodality therapy. L-[methyl-11C] methionine PET has observed high accumulation at the time of recurrence, it is important to understand the mechanism of tumor cell activation caused by the reorganization of methionine metabolism. Methods We cultured cells in methionine-deprived culture medium for comprehensive analysis. Based on the obtained results, the possible target molecules were chemically inhibited and the respective markers were analyzed. Results Methionine depletion markedly decreased proliferation and increased cell death of GICs. Decreased S-adenosyl-methionine, which is synthesized intracellularly by catalyzed by methionine adenosyltransferase using methionine, triggered the following: (i) global DNA demethylation, (ii) hyper-methylation of signaling pathways regulating pluripotency of stem cells, (iii) decreased expression of the core-genes and pluripotent markers of stem cells including FOXM1, SOX2, SOX4, PROM1, and OLIG2, (iv) decreased cholesterol synthesis and increased excretion mainly through decreased SREBF2, and (v) down-regulation of the large subunit of ribosomal protein configured 28S and ACA43, small nucleolar RNA guiding the pseudouridylation of 28S rRNA, which is essential for translation. In addition, inhibition of cholesterol synthesis with statin resulted in a phenotype similar to that of methionine depletion and decreases in stem cell markers and small nucleolar RNA ACA43. Moreover, suppression of FOXM1 decreased stem cell markers such as SOX4 and PROM1. The gene expression profile for cholesterol production was obtained from the Ivy Glioblastoma Atlas Project database and compared between tumor cells with relatively low methionine levels in areas of pseudopalisading arrangement around necrosis and tumor cells in the infiltrating region, showing that cells in the infiltrating region have higher capacity to produce cholesterol. Conclusions Methionine metabolism is closely related with self-renewal, pluripotency, and cell death in GICs through modification of cholesterol biosynthesis, especially in the SREBF2-FOXM1 and ACA43 axis with modification of rRNA.

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Section: Resultsmentioning

confidence: 99%

Methionine regulates self-renewal, pluripotency, and cell death of GIC through cholesterol—rRNA axis

et al. 2022

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“…Differentially methylated bins showing at least 20% methylation level difference with Q -value (<0.05) calculated using Fisher's exact test and showing 2-fold difference were considered as DMRs. The DMRs were annotated through gene territories using GeneDMRs of R package (Wang et al, 2021b ).…”

Section: Methodsmentioning

confidence: 99%

Pup1 QTL Regulates Gene Expression Through Epigenetic Modification of DNA Under Phosphate Starvation Stress in Rice

Kumar

Seem

Kumar³

et al. 2022

Front. Plant Sci.

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Cytosine methylation, epigenetic DNA modification, is well known to regulate gene expression. Among the epigenetic modifications, 5-methylcytosine (5-mC) has been one of the extensively studied epigenetic changes responsible for regulating gene expression in animals and plants. Though a dramatic change in 5-mC content is observed at the genome level, the variation in gene expression is generally less than that it is expected. Only less is understood about the significance of 5-mC in gene regulation under P-starvation stress in plants. Using whole-genome bisulfite sequencing of a pair of rice [Pusa-44 and its near-isogenic line (NIL)-23 harboring Pup1 QTL] genotypes, we could decipher the role of Pup1 on DNA (de)methylation-mediated regulation of gene expression under P-starvation stress. We observed 13–15% of total cytosines to be methylated in the rice genome, which increased significantly under the stress. The number of differentially methylated regions (DMRs) for hypomethylation (6,068) was higher than those (5,279) for hypermethylated DMRs under the stress, particularly in root of NIL-23. Hypomethylation in CHH context caused upregulated expression of 489 genes in shoot and 382 genes in root of NIL-23 under the stress, wherein 387 genes in shoot and 240 genes in root were upregulated exclusively in NIL-23. Many of the genes for DNA methylation, a few for DNA demethylation, and RNA-directed DNA methylation were upregulated in root of NIL-23 under the stress. Methylation or demethylation of DNA in genic regions differentially affected gene expression. Correlation analysis for the distribution of DMRs and gene expression indicated the regulation of gene mainly through (de)methylation of promoter. Many of the P-responsive genes were hypomethylated or upregulated in roots of NIL-23 under the stress. Hypermethylation of gene body in CG, CHG, and CHH contexts caused up- or downregulated expression of transcription factors (TFs), P transporters, phosphoesterases, retrotransposon proteins, and other proteins. Our integrated transcriptome and methylome analyses revealed an important role of the Pup1 QTL in epigenetic regulation of the genes for transporters, TFs, phosphatases, carbohydrate metabolism, hormone-signaling, and chromatin architecture or epigenetic modifications in P-starvation tolerance. This provides insights into the molecular function of Pup1 in modulating gene expression through DNA (de)methylation, which might be useful in improving P-use efficiency or productivity of rice in P-deficient soil.

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“…Over the last decade, a number of computational approaches have been developed to identify genes that are abnormally methylated in human diseases. Some methods are tailored to the analysis of DNAme data from bisulfite sequencing, 4 , 5 , 6 , 7 while others are designed for array-based data or can be adapted to both platforms. 8 , 9 , 10 , 11 , 12 Many existing methods identify differentially methylated loci by comparing all samples from an experimental group with those from a control group.…”

Section: Introductionmentioning

confidence: 99%

EpiMix is an integrative tool for epigenomic subtyping using DNA methylation

Zheng

Jun

Brennan

et al. 2023

Cell Reports Methods

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GeneDMRs: An R Package for Gene-Based Differentially Methylated Regions Analysis

Cited by 6 publications

References 36 publications

Methionine regulates self-renewal, pluripotency, and cell death of GIC through cholesterol—rRNA axis

Methionine regulates self-renewal, pluripotency, and cell death of GIC through cholesterol—rRNA axis

Pup1 QTL Regulates Gene Expression Through Epigenetic Modification of DNA Under Phosphate Starvation Stress in Rice

EpiMix is an integrative tool for epigenomic subtyping using DNA methylation

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