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|Title:||Global DNA methylation synergistically regulates the nuclear and mitochondrial genomes in glioblastoma cells|
St John, J.
|Citation:||Nucleic Acids Research, 2018; 46(12):5977-5995|
|Publisher:||Oxford University Press|
|Xin Sun, Jacqueline Johnson and Justin C. St. John|
|Abstract:||Replication of mitochondrial DNA is strictly regulated during differentiation and development allowing each cell type to acquire its required mtDNA copy number to meet its specific needs for energy. Undifferentiated cells establish the mtDNA set point, which provides low numbers of mtDNA copy but sufficient template for replication once cells commit to specific lineages. However, cancer cells, such as those from the human glioblastoma multiforme cell line, HSR-GBM1, cannot complete differentiation as they fail to enforce the mtDNA set point and are trapped in a 'pseudo-differentiated' state. Global DNA methylation is likely to be a major contributing factor, as DNA demethylation treatments promote differentiation of HSR-GBM1 cells. To determine the relationship between DNA methylation and mtDNA copy number in cancer cells, we applied whole genome MeDIP-Seq and RNA-Seq to HSR-GBM1 cells and following their treatment with the DNA demethylation agents 5-azacytidine and vitamin C. We identified key methylated regions modulated by the DNA demethylation agents that also induced synchronous changes to mtDNA copy number and nuclear gene expression. Our findings highlight the control exerted by DNA methylation on the expression of key genes, the regulation of mtDNA copy number and establishment of the mtDNA set point, which collectively contribute to tumorigenesis.|
|Keywords:||Cell Line, Tumor; Cell Nucleus; Humans; Glioblastoma; DNA, Mitochondrial; Immunoprecipitation; DNA Methylation; Transcription, Genetic; Gene Expression Regulation; Genes, Mitochondrial; Genome, Mitochondrial; DNA Copy Number Variations; Whole Genome Sequencing|
|Rights:||© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact email@example.com|
|Appears in Collections:||Medicine publications|
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