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Research Paper

A novel role for mitochondria in regulating epigenetic modifications in the nucleus

Dominic Smiraglia, Mariola Kulawiec, Gaia L. Bistulfi, Sampa Ghoshal and Keshav K. Singh

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Epigenetic modification in the nuclear genome plays a key role in human tumorigenesis. In this paper, we investigated whether changes in the mtDNA copy number frequently reported to vary in a number of human tumors induce methylation changes in the nucleus. We utilized the Restriction Landmark Genomic Scanning (RLGS) to identify genes that undergo changes in their methylation status in response to the depletion and repletion of mtDNA. Our study demonstrates that depletion of mtDNA results in significant changes in methylation pattern of a number of genes. Furthermore, our study suggests that methylation changes are reversed by the restoration of mtDNA in cells otherwise lacking the entire mitochondrial genome. These studies provide the first direct evidence that mitochondria regulate epigenetic modification in the nucleus that may contribute to tumorigenesis.

Authors

Dominic Smiraglia

Mariola Kulawiec

Department of Cancer Genetics Roswell Park Cancer Institute

Gaia L. Bistulfi

Department of Cancer Genetics Roswell Park Cancer Institute

Sampa Ghoshal

Department of Cancer Genetics Roswell Park Cancer Institute

Keshav K. Singh

Department of Cancer Genetics Roswell Park Cancer Institute

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.