00085472can171473-sup-183491_1_supp_4101828_mrjyyd.pptx (968.74 kB)

Supplemental Figure 1 from Mitochondrial Genomic Backgrounds Affect Nuclear DNA Methylation and Gene Expression

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posted on 2023-03-31, 01:04 authored by Carolyn J. Vivian, Amanda E. Brinker, Stefan Graw, Devin C. Koestler, Christophe Legendre, Gerald C. Gooden, Bodour Salhia, Danny R. Welch

Supplemental Figure 1. Validation of Methyl-Seq and RNA-Seq. Several hypo-/hyper-methylated and down-/up-regulated genes were selected for validation using methylation specific primers (64) or quantitative PCR, respectively. Graphs depict fold-change between MNX strains and corresponding wild-type mice are shown to the left. All gene expression data were normalized to beta actin. Each bar combines pools A and B and the experiments were performed in triplicate. Error bars represent standard error. Representative gels showing unmethylated (U) and methylated (M) DNA are shown. The table summarizes specific genes tested and whether the RNA-or Methyl-Seq data were and were not validated.

Funding

Susan G. Komen for the Cure

NIH

History

ARTICLE ABSTRACT

Mitochondrial DNA (mtDNA) mutations and polymorphisms contribute to many complex diseases, including cancer. Using a unique mouse model that contains nDNA from one mouse strain and homoplasmic mitochondrial haplotypes from different mouse strain(s)—designated Mitochondrial Nuclear Exchange (MNX)—we showed that mtDNA could alter mammary tumor metastasis. Because retrograde and anterograde communication exists between the nuclear and mitochondrial genomes, we hypothesized that there are differential mtDNA-driven changes in nuclear (n)DNA expression and DNA methylation. Genome-wide nDNA methylation and gene expression were measured in harvested brain tissue from paired wild-type and MNX mice. Selective differential DNA methylation and gene expression were observed between strains having identical nDNA, but different mtDNA. These observations provide insights into how mtDNA could be altering epigenetic regulation and thereby contribute to the pathogenesis of metastasis. Cancer Res; 77(22); 6202–14. ©2017 AACR.