American Association for Cancer Research
00085472can171473-sup-183491_1_supp_4101830_frjyyd.pptx (2.47 MB)

Supplemental Figure 3 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 3. Integrative analysis of methylation and gene expression. The methylation level for the five most differentially expressed genes (listed at the top of each page), for which also methylation data was available, is shown in Panels A-E for each gene. Chromosomal position of the corresponding gene is shown on the x-axis, and the methylation in percentage is shown on the y-axis. Each star represents one CpG. CpG''s for BB are shown in green, while CpG''s for FB are shown in orange. For both types a LOWESS (Locally Weighted Scatterplot Smoothing) smoother was used to create a "regression line". The boxplot in panel F for each gene presents the normalized gene expression for both samples (BB and FB) for the five previously picked genes. Again, green indicates a BB-sample and orange indicates a FB-sample. Each box visualizes two normalized gene expressions (two replicates).


Susan G. Komen for the Cure




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.