A novel role for mitochondria in regulating epigenetic modification in the nucleus.
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.
Smiraglia
Dominic J
DJ
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Kulawiec
Mariola
M
Bistulfi
Gaia L
GL
Gupta
Sampa Ghoshal
SG
Singh
Keshav K
KK
D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D023281:Genomics / Q000379:methods; D006801:Humans; D006822:Hybrid Cells; D008928:Mitochondria / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins